TW200529810A - Proteasome inhibitors and methods of using the same - Google Patents

Abstract

The present invention provides boronic acid compounds, boronic esters, and compositions thereof that can modulate apoptosis such as by inhibition of proteasome activity. The compounds and compositions can be used in methods of inducing apoptosis and treating diseases such as cancer and other disorders associated directly of indirectly with proteasome activity.

Description

200529810 IX. Description of the invention: [Technical field to which the invention belongs] The present invention relates to a compound that can be used as a protein degradation inhibitor and to modulate cell decay. [Previous technology] Protein degradants (also known as multi-catalytic proteinases (MCP), multi-catalytic proteases, multi-catalytic protease complexes, multi-catalytic endopeptidase complexes, 20S, 26S or gibbins) It is a large multi-protein complex that exists in both the cytoplasm and the nucleus of all eukaryotic cells. It is a highly conserved cell structure responsible for ATP-dependent proteolysis of most cellular proteins (Tanaka, Biochem BiOjphy · Res · Commun; 1998, 247, 537). The 26S protein degradation system contains a 20S core catalytic complex, which is terminated at each end by a 19S regulatory subunit. The protozoan 20S protein degradation product contains fourteen copies of two different types of subunits α and / 3, which form a cylindrical structure containing four stacked rings. The top and bottom rings each contain seven α-subunit φ positions, while the inner ring contains seven rash subunits. The more complex 20S protein degradation system of eukaryotic cells is composed of about 15 different 20-30 kDa subunits, and its characteristics are three main activities related to peptide substrates. For example, proteolytic enzymes show trypsin-, chymotrypsin- and peptidylglutamine-peptidyl-hydrolytic activity (Rivett, So //, 1993, 29 /, 1 and Orlowski, Soc / zemz · 1990, 29, 10289). Furthermore, protein degradants have a unique active site mechanism, and it is generally considered that they use threonine residues as nucleophilic groups for catalysis (Seemuller et al., 1995, 2 Milk, 579). The 26S protein degradation system is capable of degrading proteins that have been removed by adding ubiquitin molecules. Typically, ubiquitin is linked to the lysine of lysine in a multi-step process using Ατρ and ei (ubiquitin activation) 舁 E2 (ubiquitin conjugate) enzymes. The ubiquitinated protein is recognized by the 26S protein degradants and is degraded. Polyubiquitin chains are generally released from the complex and recovered from ubiquitin (Goldberg et al., Shi Qing, 1992, 357, 375). «Midnight withered protein is a substrate for ubiquitin-dependent proteolysis. Many of these proteinaceous shells serve as a regulator of physiological and pathophysiology of cellular processes. The change in proteolytic activity is involved in a variety of pathological diseases including neurodegenerative diseases such as Parkinson's disease, Alzheimer's 'S disease and occlusive / haemic reperfusion injury, and aging of the central nervous system. The ubiquitin proteolytic pathway also plays a role in neoplastic growth. It is recognized that the regulation and degradation of proteins such as cyclins, CDK2 inhibitors and tumor suppressors is important in cell cycle progression and mitosis. The protein degrading species is known to be a tumor suppressor p53, which is involved in several cellular processes (see, e.g., K, L. J. Cong, 1996, Sichuan, 105). Tumor Lu M inhibitor P53 has been shown to cause cells in several hematopoietic cell lines> Zhou Ling (0, M ·, & Kan, Guan, 5,221). ρ53 causes cell growth arrest in the G1 phase of the cell cycle and cell death due to cell death. It is known that the degradation of the tumor suppressor ρ53 is carried out via the ubiquitin-protein degrader pathway, and that the degradation of ρ53 degradation by the inhibition of protein degraders is a possible mode that causes cell decay. Proteolytic bodies are also required to degrade the inhibitory protein I / cB of the transcription factor NpB to activate it (Pak) mbel] [a et al. 1994, 75, corp. 3). NF-a: B plays a role in the transcription of cell death inhibitors to keep cells alive 95014 200529810. Blocking of NF- / cB activity has been shown to make cells more susceptible to> zero weeks.

Several inhibitors of the proteolytic activity of proteolytic bodies have been reported. See, for example, Kisselev et al., Yun Xueyu Zhichang #, 2001, & 739. Lactcystine is a metabolite of the genus Streptomyces, which specifically inhibits the proteolytic activity of the proteolytic complex (Fenteany et al., 5W Carcass 1995, 2 Paper 726). This molecular line is capable of inhibiting the proliferation of several cell types (Fenteany et al., / Voc. Mzi /. 1994, 97, 3358). It has been shown that lactate can pass through its / 3-lactone moiety to irreversibly bind to a threonine residue at the amine end of the protein subunit. Peptide aldehydes have been reported to inhibit chymotrypsinogen-like activity associated with protein degradants (Vinitsky et al., 5A cAe and 1992, 37, 9421; Tsubuki et al., Shen Xinsuo · Noisy / ^ 7? From Cbmm Jump, 1993, 7P (5, 1195; and Rock et al., Ce //, 1994, 7S, 761). Dipeptidyl acid inhibitor with IC50 in vitro in the range of 10.100 nM (Iqbal, M., et al., J. Med. Chem., 1995, 35, 2276) have also been reported. Derived from α-ketocarbonyl and a series of dihydroxyborane-derived dipeptides are equally effective in vivo External inhibitors have also been reported (Iqbal et al., Bioorg. Med. Chem. Lett., 1996, 6, 287, Jl: ® -f- 5,614,649; 5,830,870 »5,990,083; 6,096,778; 6,310,057; US Patent Application Gazette 2001 / 0012854 and WO 99/30707). N-terminal peptidyl dihydroxyborane esters and acid compounds have been previously reported (U.S. Patent Nos. 4,499,082 and 4,537,773; WO 91/13904; Kettner et al., C.O. 1984, 259 (24), 15106). These compounds are reported to be inhibitors of certain proteolytic enzymes. N-terminal tri-peptide dihydroxyborane And acidification 95014 200529810 compounds have been shown to inhibit the growth of cancer cells (U.S. Patent 5,106,948) ° — A broad class of N-terminal tri-peptide dihydroxyborane esters and acid compounds and their analogs have been injected Inhibits Renhaohaosu (U.S. Patent 5,169,841) °

Various inhibitors of proteolytic peptidase activity have also been reported. See, for example, Dick, et al., 1991, 30, 2725; Goldberg et al., Nature, 1992, 357, 375; Goldberg, Eur. 1 Biochem.f 1992, 203, 9 \ Orlowski, Biochemistry, 1990, 29, 10289; BAvetX et al., Archs · Biochem · Biophys ·, 1989, 2/5, 1; Rivett et al., · 5 Magic / · 1989, 2 ^, 12215; Tanaka et al., New Biol "1992, 4, 1 ·, MamkRmi et al., Proc. Natl. Acad. Sci. USA, 1986, 53, 7588; Li et al., 5 Magic c / zem Fen 1991, 30, 9709; Goldberg, Ar. J. Biochenu, \ 991, 203, 9 ·, Sl special k, protease and biological control,

Cold Spring Harbor Laboratory Press (1975), pages 429-454.

U.S. Patent Application Serial No. 08 / 212,909 filed by Stein et al. On March 15, 1994, reports that peptide aldehydes can be used in animals to reduce the rate of muscle mass loss and the rate of intracellular protein breakdown. These compounds are also said to reduce the rate of p53 protein degradation in animals. Palombella et al., WO 95/25533 report the use of peptide aldehydes by contacting animal cells with peptidaldehyde inhibitors that function as protein degraders or ubiquitin to reduce cell content in animals and NF- / cB activity. Goldberg and Rock, WO 94/17816 report the use of proteolytic inhibitors to inhibit MHC-I antigen presentation. Stein et al., U.S. Patent No. 5,693,617 report that peptidyl aldehyde compounds as inhibitors of protein degradants can be used to reduce the rate of protein degradation in animals. Inhibition of 26S and 20S protein degradants by hydroindone derivatives and methods for inhibiting cell proliferation using hydroindone derivatives, by Lum 95014 200529810

Et al., U.S. Patent 5,834,487 report. In mammals, alpha-ketamine compounds that can be used to treat disorders mediated by 20S protein degraders are reported in Wang et al., U.S. Patent 6,075,150. France et al., WO 00/64863 report the use of 2,4-diamino-3-hydroxycarboxylic acid derivatives as inhibitors of protein degradation products. Carboxylic acid derivatives as inhibitors of protein degradation are reported by Yamaguchi et al., EP 1166781. Ditzel et al., EP 0995757, report bivalent inhibitors of protein degradation. A 2-aminobenzyl nystatin derivative that non-covalently inhibits the chymotrypsinogen-like activity of a 20S protein degradant has been described by Garcia-Echeverria et al., ⑽rg · Med C / zern · Zd 2001, 7 /, 1317 report. Some other proteolytic inhibitors may contain a boron moiety. For example, Drexler et al., WO 00/64467 report a method for selectively using a protein degradant inhibitor containing a tetrapeptide dihydroxyboranoate in activated endothelial cells or leukemia cells with high expression levels of c-myc Methods that cause cells to wither. Furet et al., WO 02/096933 report 2-[[N- (2-Amino-3- (heteroaryl or aryl) propylamido) aminoamido] amino] alkyldihydroxyborane and esters Class' In warm-blooded animals, for the treatment of proliferative diseases. U.S. Patents 6,083,903; 6,297,217; 5,780454; 6,066,730; 6,297,217; 6,548,668; U.S. Patent Application Publication 2002/0173488; and WO 96/13266, reports dihydroxyboronate and acid compounds, and a method for reducing the rate of protein degradation. A method for inhibiting viral replication using certain dihydroxyboranes and esters is also reported in U.S. Patents 6,465,433 and WO 01/02424. Pharmaceutically acceptable compositions of dihydroxyborane, novel dihydroxyborane anhydrides, and dihydroxyborane ester compounds are reported by Plamondon et al., U.S. Patent Application Gazette 95014-10-200529810 2002/0188100. In Gardner et al., OcAem ···, 2000, 447, Yan Zhengshi is a series of two- and two-derived dimer radicals, which are inhibitors of 20S and 26S protein degradation products.

Other peptide-containing and related compounds are reported in U.S. Patents 5,250,720; 5,242,904; 5,187,157; 5,159,060; 5,106,948; 4,963,655; 4,499,082; and WO 89/09225, WO 98/17679, WO 98 / 22496, WO 00/66557, WO 02/059130, WO 03/15706, WO 96/12499, WO 95/20603, WO 95/09838, WO 94/25051, WO 94/25049, WO 94/04653, WO 02 / 08187, EP 632026 and EP 354522. As confirmed by the above reference materials, there is a great interest in drugs that can modulate the activity of protein degraders. For example, molecules capable of inhibiting the activity of protein degraders can suppress or delay cancer progression by interfering with the regular degradation of cell cycle proteins or tumor suppressors. Therefore, there is an ongoing need for novel and / or improved proteolytic inhibitors. [Summary of the Invention]

The present invention is directed to novel dihydroxyborane and dihydroxyborane ester compounds which can be used as inhibitors of protein degradants and cell decay regulation. The invention also includes methods of inhibiting a multi-catalytic protease (' MCP ') associated with certain conditions, including the treatment of muscle wasting conditions. In one embodiment, a compound having formula (I) is provided:

95014 -11-200529810 The members and preferred members are defined below. In another specific embodiment, the present invention provides a pharmaceutical composition comprising a compound of formula (1) and a pharmaceutically acceptable carrier. σ In another embodiment, the present invention provides a method for inhibiting the activity of a protein degrading body ', which comprises contacting a compound of formula ① with the protein degrading body. In another embodiment, the present invention provides a method for treating cancer, which comprises administering to a mammal having or susceptible to the cancer a compound of formula (I) which is therapeutically effective. In another specific embodiment, the present invention provides a method for treating cancer, which comprises administering a therapeutically effective amount of a compound to a mammal having or susceptible to the cancer, and wherein the cancer is selected from the group consisting of skin, Prostate, colorectal, viscera, kidney, ovary, breast, liver, tongue, lung and smooth muscle tissue. In another specific embodiment, the present invention provides a method for treating cancer, which comprises administering to a mammal having or susceptible to the cancer a therapeutically effective amount of a compound of formula (I), and wherein the cancer is selected from the group consisting of Leukemia, lymphoma, non-Hodgkin lymphoma, myeloma, and multiple myeloma. In another specific embodiment, the present invention provides a method for treating cancer, which comprises administering a therapeutically effective amount of a compound of formula (I) to a mammal having or susceptible to the cancer, and using one or more antitumor agents Or anticancer agents and / or radiation therapy. In another specific embodiment, the present invention provides a method for inhibiting the activity of the transcription factor nf_ / cB, which comprises uB, an inhibitor of the transcription factor 1 ^ _, 95014 -12- 200529810 and a compound of formula (I) Angle | In another embodiment, the present invention provides a method for preparing a compound of formula (ιι): R1

I H2C,

r15c1 〇 ⑻ Where the group injury members are defined herein, the way is to make the formula (n_b) diol:

HO HOv / Ri5a

r15c ', Rl5b / pq (Il-b) is reacted with a trialkoxyborane of the appropriate formula (II-a): R17〇 / OR17 OR17 (II-a) where the component members are defined herein; in Suitable time and conditions for forming intermediates of formula (n_c):

P / Rl5a ‘R15b

D

R 15c I (Hc) q and make the intermediate of formula (II-c) at a time and conditions suitable for the formation of a compound of formula (II) 95014 • 13- 200529810, and whether it is i) formula Ria ^ MX1 ^ 1 reagent, Wherein M is a metal and xhal is a halogen atom, or ii) the reaction of a reagent of formula R1 CH2Li. These and other features of the compounds will be presented in an expanded form as disclosed in the continuation. Description of specific embodiments of the invention

The present invention particularly provides compounds which inhibit the activity of proteolytic enzymes and are useful for treating diseases or conditions associated with the activity of proteolytic enzymes. The compounds of the present invention include compounds of formula (I) OR2 (I) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein R1 is CrC8 alkyl, c2-c8 alkenyl, c2- c8 alkynyl or c3-c7 cycloalkyl; R2 is Η,-(CH2) aCH2NHC (= NR4) NH-Y,-(CH2) bCH2CONR5R6,-(CH2) c CH2 N (R4) CONH2,-(CH2) d CH (R7) NR9 R10 or-(CH2) eCH (R7) ZR8; a, b, and c are each independently 0, i, 2, 3, 4, $, or 6; d and e are each independently 0, 1, 2, 3, or 4; R4 is fluorene or Ci-Cio alkyl; R5 and R6 are each independently fluorene, radical, carbocyclyl, heterocarbocyclyl or amine protecting group; or 'R5 is connected to ^ Atom—starts to form a heterocarbocyclic group; R7 is only or fluorenyl; 95014 -14- 200529810 R8 is fluorene, CAo alkynyl, alkynyl_s (= 〇) 2_, aryl_s (= 〇 ) 2_, H2NS (= 0) 2-, -S03H or protecting group; R9 is fluorene, q-qo alkyl, carbocyclic or heterocarbocyclic group; R10 is fluorene, (VC1 () alkyl, carbocyclic group , Heterocarbocyclyl, Ci_CMalkyl-c (= o)-, c2 a 〇alkenyl_c (= 0) _, C2_Ci alkynyl_c (= 〇), carbocyclyl-C (= 0)-, heterocarbocyclyl-C (= 0 >, carbocyclylalkyl ((= 〇) Heterocarbocyclyl-c (= 0)-, Cl-Cl 〇alkyl-SK >) 2 _, carbocyclyl wool (= 0) 2 _, • heterocarbocyclyl-S (= 0) 2 ... carbocyclylalkyl-s (= 0) 2-, heterocarbocyclylalkyl ginseng-SH)) 2_, c "c1 () alkyl-NHC (= 0 >, carbocyclyl c (= 〇 ) ... heterocarbocyclyl-NHCH3)-, carbocyclylalkyl ... heterocarbocyclyl-NHC (= 0)-, Q-C! 〇alkyl_〇C (= 〇) _, carbocyclyl Heart c (= 〇) _, heterocarbocyclyl-oc (= o)-, carbocyclylalkyl_0C (= 0>, heterocarbocyclylalkyl-〇C (= 0)-, CVCw alkyl -NH-C (= 0) -NHS (= 0) 2-, carbocyclyl_NH-C (= 0) _NHS (= 0) 2-, heterocarbocyclyl,

Ci -C! 〇 Alkyl-S (= 0) 2 -NH-C (= 0)-, carbocyclyl_s (= 0) 2 -NH-C (= 0)-, heterocyclic carbocyclyl- S (= 〇) 2-NH-C (= 0)-or amine protecting group; wherein R1. It is optionally substituted by 1, 2 or 3 R23; or 'R9 forms a heterocarbocyclic group with Rio and the N atom to which they are connected, which is optionally substituted by 1, 2 or 3 R23; Y is Η, _CN, -N02, -S (= 0) 2Ru or guanidino protecting group; RU is cvc6 alkyl, aryl or NR12R13; R and R13 are independently fluorene, G-Ci alkynyl, carbocyclic, Heterocarbocyclic or amine protecting group; or, R12 forms a heterocarbocyclic group together with Ri3 and the N atom to which they are attached; 95014 -15- 200529810 z is 0, s, Se or Te; Q is -B ( OH) 2, -BCOR1 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains a hetero atom which can be N, S or 0; R14 is H, CrC4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; X is RAC (= 0) _, RANHC (= 0) ... RAS (= 〇) 2_, RAochQ)-, # % (= 〇) _ or RA;

RA is a CrCw alkyl group optionally substituted by R2G; a C2-C2G alkenyl group optionally substituted by R2G; a C2-C2Q alkynyl group optionally substituted by R2G; a carbocyclic group substituted by 1-5 R21 as appropriate; Or optionally a heterocarbocyclic group substituted with 1-5 R21; & 2 () is selected from the group consisting of: -CN, halo, haloalkyl-, Ci -C4 alkyl, C〗 -C4 dilute radical, C2 -C4 Fast radical, -CO2H, -C (= 0) C〇2H, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2 , -OH, -SH, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0) R2Ga, -NHC (= O) OR20a,- OR20a, -SR20a, -S (= O) R20a, -S (= O) 2R20a, -S (= 〇) 2-NHR20a, -SC (= O) R20a ^ -C (= O) R20a > -C (= O) NHR20a ^ -C (= 0) 0-R2 0 a '-NHS (= O) 2R20a, -NHR20b, phthalimide,-(0-alkyl) r-OH, ·· (0-alkyl) r- (0-alkyl), -OR2Gc, -SR20c, -O-alkyl. R2oc, -S-alkyl-R20c, -S (= O) -R20c,- s (= o) 2-r2〇c, -S (= O) 2-NHR20c, -sc (= o) r20c, -c (= o) r20c, -C (= O) OR20c, -C (= 0 ) NHR2Ge, a carbocyclic group substituted with 1-5 R21 as appropriate; and a heterocarbocyclic group substituted with 1-5 R2 1 as appropriate, 950U -16-200529810; ^ 2 { ) & is (: 1 <: 20 alkyl, (: 2-(: 20 alkenyl, or (: 2 (2 () alkynyl); where the alkyl, alkenyl, or alkynyl group is optionally one or more Halo, OH, CN, C! -C4 alkyl, alkoxy, C2-C8 alkoxyalkoxy, aryl, heteroaryl or -NHR2Gb substitution; R2 () b is an amine protecting group; R2Ge is a carbocyclic group optionally substituted with 1 to 5 R22; or

Heterocarbocyclic groups substituted with 1 to 5 R22 as appropriate; R21 is selected from the group consisting of: (VCw alkyl, C2-C2G alkenyl, C2-C2G alkynyl, -OR21a, _SR21a, -CN, halo, halo Alkyl, -NH2, -NH (alkyl), -N (alkyl), -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -COOH, -C (= 0) 0-alkyl, -C (= 0) alkyl, -C (0) H, -S (= 0) -alkyl, _S (= 0) 2-alkyl, -S (= 0) -aryl , -S (= 0) 2-aryl, carbocyclyl substituted with 1-5 R2 2 as appropriate and heterocarbocyclyl substituted with 1-5 R22 as appropriate; 1121 & is 11, CrC2〇alkane Group, C2-C20 alkenyl, C2-C20 alkynyl, carbocyclyl or heterocarbyl, R22 is selected from the group consisting of: CVCw alkyl, c2-c10 alkenyl, c2-c10 alkynyl, phenyl , Halo, haloalkyl, alkoxy, thioalkoxy, amine, amine, diamine, carboxyl, alkyl-oc (= o)-, alkyl-c (= 0) -, Aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C ( = 0) 0-, (alkyl-〇) r-alkyl, HO_ (alkyl_0) r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl -S (= 0) _, alkyl-S (= 0) 2-, 95014 -17- 200529810 H2 NS (= 0)-and H2 NS (= 0) 2-; R23 is selected from the group consisting of: CVQ alkyl, C2-C6 alkenyl, (: 2-(: 6 alkynyl, F, Cl, Br, I, haloalkyl, -NΗ2, -NHR23a, -N (R23a) 2, -N3, -N〇2, -CN, -CNO, -CNS, -C (= 0) 0R23a, -C (= 0) R23a, -0C (= 0) R23a , -N (R23a) C (= 0) R23a, -N (R23a) C (= 〇) 〇R23a, -C (= 0) N (R23a) 2, Urea group, -OR23a, -SR23a, -s (= o) 2- (cvc6 Φ alkyl), -S (= 0) -aryl, -S (= 0) 2-aryl, -S (= 0) 2-N (R23a) 2; see_ Carbocyclyl substituted by 1-5 R24 in some cases; and heterocarbocyclyl substituted by 5 R24 if appropriate; & 233 is "[or CVC6 alkyl; or 'Two R23a can be with them The connected N atoms are combined together to form a 5- to 7-membered heterocyclic group; and 夂 24 is selected from the group consisting of: cvqalkenyl, C2-C4 alkenyl, C2-C4 alkynyl, phenyl, Halo® alkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, arsinocarboxy, alkyl-OC (= 〇) _, alkyl-c (= 0)-, Aryl-OC (= 0)-, alkyl_0C (= 0) NH-, aryl_0C (= 0) NH-, alkyl-C (= 0) NH o) a, (Carbonyl-0) r_alkyl, Ηα (alkyl-〇) r_alkyl-, OH -SH, -CN, -N3, _CNO, -CNS, alkyl-SH))-, alkyl-S (= 0) 2-, H2 NS (= 〇)-, and H2 NS (K)) 2-; And r is 1,2,3,4,5,6,7,8,9 or 10; with the condition that when Q is 1,1,2,2-tetramethylethanediol dihydroxyboron For alkyl esters, then X is not an aralkyloxycarbonyl group; 95014 • 18-200529810 with the proviso that when Q is U, 2,2-tetramethylethanediol dihydroxyborane, and R1 is In the case of a cycloalkyl group, then R2 is not -CH2c0NH2; and the conditions are 'when X is RAC (= 〇)-, RA is a C4_Cu straight chain alkyl group substituted with 圮 〇' and R2〇 is- CN, -C02 Η, -C (= 0) 0-R2 0 a, -NHS (= 0) 2R2 () a, -NHCH)) R20a, -NHR2〇b or phthalimide imide; Then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where γ is Η, -CN, -N02 or a guanidino protecting group. In a further specific embodiment, when R2 is _ (CH2) eCH (R7) ZR8, e is 0, R7 is Η, R8 is Q alkyl, and X is rA c (= 〇) _, then rA is not It is aminoalkyl-, alkylaminoalkyl-, dialkylaminoalkyl- or ureidoalkyl. In some embodiments, R1 may be Cl-C4 alkyl, and in further specific embodiments, R1 may be propyl, such as 2-propyl. In some specific embodiments, R2 can be _ (CH2) aCH2NHC (= NR4) NH_Y,-(CH2) bCH2CONR5R6,-(CH2) cCH2N (R4) CONH2,-(CH2) dCH (R7) NR9 R10, or-( CH2) eCH (R7) ZR8. In some embodiments, R2 is-(CH2) aCH2NHC (= NR4) NH-Y, and a is 1, 2, 3, 4 or 5. In some specific embodiments, R2 is _ (CH2) aCH2NHC (= NR4) NH_Y, and a is 2. In some specific embodiments, R2 is _ch2ch2ch2nhc (= nr4) nh-y. In some embodiments, R2 is _ (CH2) dCH (R7) NR9Ri 〇, and d is 0, 1, or 2 〇 In some embodiments, R2 is _ (CH2) dCH (R7) NR9Ri 〇, and d is 0. In some specific embodiments, R2 is · (CHACHCR ^ NR9! ^ 0, and R9 is 95014-19.200529810). In the embodiments, R2 is < CH2) dCH (R7) NR9R10. In some embodiments, R2 is -CH (R7) NR9R10. In a specific embodiment, R2 is _CH2NH-C (K)) OCH2 (C6H5). In some gas-powered implementations, in the first embodiment, R2 is _ (CH2) ecH (R7) ZR8, and e is 0, 1, or 2 〇

In the example of He Guan Fang, R2 is < CH2) eCH (R7) ZR8, and e is 0. In some JL moved a

In the embodiment, 1 ^ 2 is _ (CH2) eCH (R7) ZR8. In some distinguished and problematic embodiments, R2 is _CH (R7) ZR8. In the specific example of step H, Z is 0. In a specific embodiment, Q has the formula (II-a):

(H_a) where D, R15a, "a", R5b, R15c, R15d, P, and q are defined below. In the specific embodiment, Q is b (oh) 2 or a cyclic dihydroxyborane ester Wherein, if this _, # a clothes-like monohydroxyborane ester contains 6 to 10 carbon atoms, and contains at least one cycloalkyl partial group. In a further specific embodiment, Q is B (OH) 2. In a further specific embodiment, Q is a pinanediol dihydroxyborane ester. In a further specific embodiment, Q is a dicyclohexyl-1,1L diol dibasic pentyl ester. 95014 -20- 200529810 Q is 1,2-dicyclohexyl_ethane], a diol dihydroxyborane ester in a further specific embodiment.

Or, in some specific embodiments

Where Q is -b (oh) 2, -b (or14) 2,

丫 （CH2) p 〇 / NH (CH2) q where: P and q are defined as follows ^ R14, R15a, R15b, R15c, R15d, w, wl. In a further specific embodiment, Q is:

W is a substituted or unsubstituted 2C4-Cl () cycloalkyl ring. In some embodiments, X is rAc (= 0) _. In some specific embodiments, X is ranhc (= 0>. In some specific embodiments, X is ras (0) 2 ... In some specific embodiments, RA is benzyl group) r-OH Or 乂 〇, alkyl) Γ- (0-alkyl) substituted CrC14 alkyl, wherein r is 1, 2, 3, 4 or 5. In some embodiments, rA is an alkyl group) r_0H or _ (〇_

950U -21-200529810) Cr- (0-alkyl) substituted CrC14 alkyl, where r is 1, 2 or 3. In some embodiments, RA comprises at least one -CH2CH20- group. In some specific embodiments, RA is -CH2 (OCH2CH2 \ OCH3. In some specific embodiments, Ra is -CH2OCH2CH2OCH2CH2OCH3 or -ch2och2ch2och3. In some specific embodiments, RA is aryl or heteroaryl, each of which depends on The situation is replaced by 1-5 R21.

In some embodiments, RA is cycloalkyl or heterocycloalkyl, each of which is optionally substituted with 1-5 R21. In some specific embodiments, # is (^-(: 20 alkyl; C2-C20 alkenyl; or c2-c2 () alkynyl, each optionally substituted by R2G. In some specific embodiments, alkyl; c2-c20 alkenyl; or C2-C2G alkynyl, each substituted with a carbocyclyl or heterocarbocyclyl, wherein the carbocyclyl or heterocarbocyclyl is optionally substituted with 1, 2, or 3 R2 1. In some specific embodiments, RA is a CVQo alkyl group; a C2-C20 alkenyl group; or a C2-C20 alkynyl group, each of which is substituted with an aryl group, wherein the aryl group is optionally substituted with 1, 2, or 3 R21. In some In a specific embodiment, RA is (VC20 alkyl group; C2-C20 alkenyl group; or C2-C20 alkynyl group, each of which is substituted by a heteroaryl group, wherein the heteroaryl group is optionally 1, 2 or 3 R2 1 In some specific embodiments, ra is an eve "alkyl group; a C2-C20 alkenyl group; or a C2 < 20 alkyl group each substituted with a alkynyl group, wherein the trivalent radical is optionally 1, 2 or 3 R2 1 substitutions. In some specific embodiments, 1 ^ is (^ -020 alkyl; C2-C20 alkenyl; or 95014 -22- 200529810 c2-c2Q alkynyl, each by a heterocycloalkyl Substitution, in which the heterocyclic alkyl group is optionally taken by 1, 2 or 3 R 2 1 In some specific embodiments, RA is CVCm alkyl; C2-C20 alkenyl; or C2-C20 alkynyl, each optionally substituted by R2G, where R2G is selected from CN, halo, haloalkyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (0) NH2, -S (0) 2NH2, _OH, -SH '-NH2,- NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= O) R20a, -NHC (= O) OR20a, -OR20 ^^ -S (0) R2 0 a , -S (0) 2 R2 0 a, _s (0) 2 -NHR2 0 a, -SC (= 0) R2 0 a, -C (= 0) R2 0 a, -C (= O) NHR20a,- C (= O) 〇-R20a, -NHS (O) 2R20a, -NHR20b, phthalimide,-(〇_alkyl),-(aalkyl) r-OH,-(〇 -Alkyl) r_ (o-alkyl), -OR2Gc, -SR2Gc, -0-alkyl-r2〇c, -s-alkyl-R20c, -S (O) -R20c, -S (O) 2- R20c, -S (O) 2, NHR20c, -SC (= O) R20c > -C (= O) R20c, -C (= 0) 0R2 G c and -C (= 0) NHR2 0 c. In some In a specific embodiment, r2 is h, and x is (a alkyl)-(0-alkyl) r-(Ci A 4 alkyl), or -0- (alkyl_0) r _ (Ci- Ci 4 alkyl) -c (= 0) _. In some embodiments, X is RAqo)-and RA is c4-Ci6 alkyl. In some embodiments, XaRAC (= 0)-, and # is an aryl group optionally substituted by u R2 1. In some embodiments, X is rac (= 0)-, and # is a heterocarbocyclic group optionally substituted with 1-3 R2 1. In some embodiments, X is RAC (= 0> RA is phenyl substituted with a fluorene 1; and R21 is phenyloxy. In some embodiments, X is RAC (= 0)-, RA Is a Cl-C4 alkyl group substituted with R2O, and R2G is an aryl group optionally substituted with 1-3 R21; and in 95041 -23- 200529810, the specific example is that the aryl group is replaced by at least one _ In some specific embodiments, X is RAC (= 〇); RA is Ci-C14 alkyl substituted by R2O; and R20 is -0R20a or _〇r20c. In some specific embodiments, X is rAc (= 〇)-; RA is an alkyl group substituted with r2O; and R2G is a heterocarbocyclic group optionally substituted with 1 to 3 1121. In some embodiments, X is Ras (0) 2- , And ... is a alkyl group. In some specific embodiments, the present invention provides a compound of formula ①, wherein the stereochemical system has the formula (Is):

(I-s) or its pharmaceutically acceptable salt form. In some embodiments, the present invention provides a compound of formula ①

(I) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is a CrC8 alkyl group, a C2-C8 alkenyl group, a C2-C8 alkynyl group, or a 0: 7 cycloalkyl group; R2 is Η,-(CH2) aCH2NHC (= NR4) NH-Y,-(CH2) bCH2CONR5R6,-(CH2) c CH2 N (R4) CONH2,-(CH2) d CH (R7) NR9 R10 or-(CH2 ) eCH (R7) ZR8; 95014 -24-200529810 a, b and c are each independently 0, 1, 2, 3, 4, 5 or 6; d and e are each independently 0, 1, 2, 3 or 4; R is fluorene or Ci-Ci0 alkyl; R5 and R6 are each independently fluorene, alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or, R5 and R6 together with their attached atoms form a hetero Carbocyclyl; R7 is fluorene or cvcw alkyl; • R8 is fluorene, C1_C1 () alkyl, alkyl-S (K)) 2_, aryl_s (= 〇) 2_, H2NSH)) 2_, -S03H Or protecting group; R is fluorene, Qo alkyl, carbocyclyl or heterocarbocyclyl; R10 is fluorene, Ci-Cw alkyl, carbocyclyl, heterocarbocyclyl, alkyl-CH) >, carbon Cyclo-CH) >, Heterocarbyl_c (= 0 >, Carbocyclyl-C (K)), Heterocarbylalkyl_c (= 0 > _s (== 〇h_, carbocyclyl-S (= 0) 2 ... heterocarbocyclyl-S (= 0) 2 ... carbon Alkyl_s (= 〇) 2_, heterocarbocycloalkyl-S (= 0) 2_, CVCmalkyl_NHC (= 〇) _ 'carbocyclyl • _NHC (= 〇)-, heterocarbocycle -NHC㈣ ... Carbocyclylalkyl-NHCd, heterocarbocyclylalkyl-NHCH))-, Cl-C1Galkyl_OCK)) _, carbocyclyl OCH))-, heterocarbocyclyl_0C (= 0) _, carbocyclylalkyl_oc (== 〇), heterocarbocyclyl-oc (= o)-, or amine-protecting group; where R10 is 1, 2, or 3 as appropriate R2 3 substitution; or, R9 and the atom to which they are attached together to form a heterocarbocyclic group; Y is -H, -CN, -N0 2 '_s (= 〇) 2Rll or guanidyl protecting group; RllgC1- C6 ^ *, ** 4NR12R13;

Rl2 and R13 are independently a fluorene, a heart-heart group, a carbocyclyl group, a heterocarbocyclyl group or an amine 95014 -25-200529810 protecting group; or, the N atoms to which they are attached together form a heterocarbocyclic group; Z is 0, S, Se or Te; Q is -B (OH) 2, -B (OR14) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms And optionally contains a heteroatom that can be N, S or 0; R14 is H'q-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; Φ x is RAc (= 〇)-, Ranhc (= o)-, ras (= 0) 2 ·, rA〇c (= 〇) _, rAsc (= 〇) _, or Ra; RA is an alkyl group substituted with r2G as appropriate; as appropriate C2-C2G alkenyl substituted by R2G; C2-C2G alkynyl optionally substituted by R2G; carbocyclyl substituted by 1-5 R21 optionally; or heterocarbon substituted by 1-5 R2 1 optionally Ring group; R2 () is selected from the group consisting of: Φ-CN, halo, haloalkyl-, CrC4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2, -OH, -SH, -NH2, -NH (alkyl), -N (Alkyl) 2, -NHC (= 0) NH2, -NHC (= O) R20a, -NHC (= O) OR20a, -OR20a, -SR20a, -S (= O) R20a, -S (= O) 2R20a, -S (= O) 2-NHR20a, _SC (= O) R20a, -C (O) R20a, -C (= 0) NHR2 () a, -C (= O) 〇-R20a, -NHS (= O) 2R20a, -NHR20b, phthalimide,-(· 〇-alkyl) r, -0- Alkyl-OH,-(0-alkyl) r-OH, -OR20c, -SR20c, -Oalkyl-R2oc, each alkyl-R2Gc, -S (= 〇) _R20e, _S (= 〇) 2_R2oe, 95014 -26- 200529810 -S (= O) 2-NHR20c, -SC (= O) R20c, -c (= o) r20c, -c (drink 20R, -C (= 0) NHR2G. Carbocyclyl substituted with 1-5 R21 as appropriate; and heterocarbocyclyl substituted with 1-5 R2 1 as appropriate; R2 0 a is Cl -C2o alkyl, C2-C2o alkenyl or C2 -C2 0 alkynyl, wherein the alkynyl, dilute or alkynyl is optionally substituted by one or more halo, C! _C4 alkynyl, aryl, heteroaryl or -NHR2Gb; fluorene is amine Protection group

R2Ge is a carbocyclic group optionally substituted by 1-5 R22; or a heterocarbocyclic group optionally substituted by 1-5 R22; R21 is selected from the group consisting of: C1-C20 alkyl, C2-C20 diaryl, 〇2 〇20 fast group, Ci-Czo alkoxy, q _C20 thioalkoxy, -OH, -CN, halo, haloalkyl, -NH2, -NH (alkyl), -N (alkyl) 2 , -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 0) 0-alkyl, -C (= 0) alkyl, -S (= 0) -alkyl , -8 (= 0) 2-carbyl, -S (= 0) -aryl, -S (= 0) 2-aryl, carbocyclic group substituted with 1-5 R22 as appropriate; and as appropriate Heterocarbocyclyl substituted with 1-5 R22; _ R22 is selected from the group consisting of:

Cl-Cl Q alkyl, C2-Cl Q dilute, C2-Cl Q fast, phenyl, 1¾, halo, oxy, thiooxy, amine, amine, diamine Alkyl, carboxyl, alkyl-oc (= o)-, alkyl-c (= o) _, aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (alkyl-0) r-alkyl, HO- (alkyl-0) r- Alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2NS (= 0)-and H2NS (= 0) 2-; 95014 -27- 200529810 R23 is selected from the group consisting of:

Ci 烧 alkyl, C2-C6 dilute, C2-C6 fast, F, Cl, Br, I, haloalkyl, -NH2, -NHR23a, -N (R23a) 2, -N3, -N02, -CN , -CNO, -CNS, -C (= 0) 0R23a, -C (= 0) R23a, -〇C (= 0) R23a, -N (R2 3 a) C (= 0) R2 3 a, -C (= 0) N (R2 3 a) 2, ureido, -OR2 3 a, -SR2 3 a, -S (= 0) 2-(A -C6 alkyl), -s (= 0) 2 _ aromatic Base and -s (= 0) 2 -N (R2 3 a) 2;

RnagHiCrQ alkyl; • Alternatively, two R23a may be combined with the N atom to which they are attached to form a 5- to 7-membered heterocyclic group; and r is 2, 3, 4, 5, 6, 7, 8, 9 or 10; and the condition is that when Q is 1,1,2,2-tetramethylethanediol dihydroxyborane ester, then X is not an aralkyloxycarbonyl group; Is' when Q is 1,1,2,2-tetramethylethanediol diacrylic acid and R1 is a cycloalkyl group, then r2 is not -CH2Conh2; and the conditions are, When X is RAC (= 0) _, ra is a c4-Ci5_ linear alkyl group substituted with R2O, and R20 is -CN, -C02H, -C (= O) O-R20a, -NHS (= 0) 2R2 () a, _NHC (= 0) R2〇a, -NHR20b or phthalimide; then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where Y is Η , -CN, -NO] or a guanidino protecting group. In some specific embodiments, Ri is 2-propyl; R2 is Η,-(CH2) aCH2NHC (= NR4) NH-Y,-(CH2) bCH2CONR5R6,-(CH2) cCH2N (R4) CONH2,-(CH2 ) dCH (R7) NR9R104 • (CH2) eCH (R7) ZR8; Q is -B (0H) 2 or pinanediol dihydroxyborane; x is RAC (= 0)-; and RA is c4-C16 Alkyl; 95014 -28- 200529810 aryl, optionally substituted with 1-3 R21; or heterocarbocyclic, optionally substituted with 1-3 R21. The present invention provides compounds of formula (I), and R1 in some specific embodiments

(I) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein:

Wgq-Cs alkyl; R2 *-(CH2) aCH2NHC (= NH) NH-Y,-(CH2) cCH2NHCONH2, even) d CH (R7) NR9 R10 or-(CH2) e CH (R7) ZR8; & Is 1, 2, 3, 4 or 5; 0 is 1, 2, 3, 4 or 5; d is 0, 1 or 2; 6 is 0, 1 or 2; R7 is fluorene or methyl; R8 is fluorene, q -Ci 0 alkyl, -S (= 0) 2-alkyl, _S (= 0) 2 aryl, -S (= 〇) 2 -NΗ2, -S03H or protecting group; Y is -Η, _CN , -N02, -SeOhR11 or a guanidyl protecting group; is fluorene, Q-Cw alkyl, carbocyclyl or heterocarbocyclyl; R10 ^ τι- stable, CVCw alkyl, carbocyclyl, heterocarbocyclyl, Ci-Ci () alkyl-c (= o >, carbocyclyl_c (= 0) _, heterocarbocyclyl < (= 〇) ... carbocyclylalkyl-CH))-, heterocarbocyclic Alkyl_c (= 0) ... Ci_Ci 〇alkyl_s (= 〇) 2 ... Carbocyclyl = 0) 2-, heterocarbocyclyl-S (= 0) r, carbocyclylalkyl -s (= 0) 2-, heterocarbocycloalkyl-S (= 0) 2-, CiAo alkyl-NHC (= 0)-, carbocycline 95014 200529810 -NHC (= 0)-, heterocarbon Cyclo-NHcpo)-, Carbocyclyl-NHC (= 〇) ... Heterocarbocyclyl-NHC (O) ... qCyridyl_OC (= 〇) ... Carbocyclyl-0C (= 0 )-, Heterocarbocyclyl-Oc (= 〇)-, carbocyclyl- 0% 〇)-, heterocarboalkyl-OC (== 0)-or an amine protecting group; wherein R1 0 is optionally substituted by 1, 2 or 3 R23; or, R9 and R1G together with the N atom to which they are attached form a heterocarbocyclic group; R11 is Ci -Cg Alkyl, aryl or NR12 R13; Φ R12 and R13 are independently fluorene, Ci-Cio alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or, R12 and R13 and the N to which they are connected The atoms together form a heterocarbocyclic group; z is 0 or s; Q is -B (OH) 2, -BiPR14) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 6 to 20 Carbon atom and containing at least one cycloalkyl moiety; R14 is fluorene, CrC4 alkyl, or cycloalkyl; x is RAc (= 〇 >, ranhc (= o)-, ras (, 2 "raoc (Which, or ra; RA is Ci-Cw alkyl optionally substituted by r2G; c2-c2G alkenyl optionally substituted by R2G; c2-c2G alkynyl optionally substituted by R2G; optionally 1-5 R21-substituted carbocyclic groups; or optionally 1-5 R21-substituted heterocarbocyclic groups; R2Q is selected from the group consisting of: -cn, halo, haloalkyl_, cvc4 alkyl, c2-c4 alkenyl , C2-C4 95014 -30- 200529810

Alkynyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2, -OH,- SH, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0) R2Ga, -NHC (= O) OR20a, -〇R20a, -SR20a , -S (= O) R20a, -S (= O) 2R20a, -S (= O) 2-NHR20a, -SC (= 0) R2〇a, -C (= 0) R2 () a, -C (= 0) NHR2 () a, -C (= O) O-R20a, -NHS (= 0) 2R2Ga, -NHR2Gb, phthalimide,-(〇-alkyl) r, -〇 -Alkyl · OΗ, · (0-alkyl) r-OH, -OR20c, -SR20c, -0-alkyl-R2Gc, -S · alkyl_R2Gc, -S (= 0) -R2Gc, -S ( = O) 2-R20c, -S (= O) 2-NHR20c > -SC (= O) R20c ^ -C (= O) R20c ^ -C (= O) OR20c ^ -C (= 0) NHR2Ge, Optionally a carbocyclic group substituted with 1-5 R21; and optionally a heterocarbocyclic group substituted with 1-5 R2 1; R2 0 a is Q-C2o alkyl, C2-C2o alkenyl or C2-C2 〇alkynyl; wherein the alkynyl, alkenyl or alkynyl is optionally substituted by one or more radicals, alkyl, aryl, heteroaryl or -NHR2Gb; 圮 ^ is an amine protecting group; R2Ge is regarded as Carbocyclyl substituted with 1-5 R22 in case; or heterocarbocyclyl substituted with 1-5 R22 in case; R21 is selected from the group consisting of:

Ci-C2G alkyl, C2-C20 alkenyl, C2-C20 alkynyl, alkoxy, Ci thiothio, -OH, -CN, halo, halo, and _N (carbo ) 2, -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, _c (= 〇) a alkyl, -C (= 0) alkyl, -S (= 0) _alkyl , -S (= 0) 2-carbon radical, _§ (= 〇)-square radical, -8 (== 0) 2- square radical, carbocyclic ring and Heterocarbocyclic groups substituted with 1-5 R22; 95014 -31-200529810 R22 is selected from the group consisting of:

Ci_Ci0 alkyl, C2-C10 dilute, C2-C10 fastyl, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, Alkyl-〇c (= o)-, alkyl-c (= 0)-, aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH ·, alkyl-C (= 0) 0-, (alkyl-0) r-alkyl, HO- (alkyl-0) r-alkyl-, -OH, -SH, -CN, -N3, _CNO, -CNS, alkyl-S (= 0) _, alkyl-S (= 0) 2-, H2NS (= 0), and H2NS (= 0) 2-; R23 is selected from the group consisting of:

Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 fastyl, F, Cl, Br, I, haloalkyl, -NH2, -NHR23a, -N (R23a) 2, -N3, -N02,- CN, -CNO, -CNS, -C (= 0) 0R2 3 a, -C (= 0) R2 3 a, -0C (= 0) R2 3 a, -N (R2 3 a) C (= 0) R2 3 a, _C (= 0) N (R2 3 a) 2, urea group, -OR2 3 a, -SR2 3 a, 4 (= 0) 2-(Cl -C6 alkyl group), -S (= 0 ) 2-aryl and -S (= 0) 2-N (R2 3 a) 2; alkyl; or, two R23 a may be combined with the N atom to which they are attached to form 5 to 7 members Heterocyclic group; and r is 2, 3, 4, 5, 6, 7, 8, 9 or 10; with the proviso that when X is RAC (= 0)-, RA is C4 substituted with R2O -Cl5 straight chain alkyl group, and R20 is -CN, _C02 Η, -C (= 0) 0_R2 0 a, _NHS (= 0) 2R2〇a, _NHC (= 〇) R20a, -NHR20l ^ phthalic acid In the case of an imino group, then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where Y is fluorene, -CN, -N02 or a guanidino protecting group. In a further specific embodiment, the present invention provides a compound of formula ① 95014 -32 · 200529810

(i) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: "is a cardio-fluorenyl; R2 is-(CH2) a CH2 NHC (= NH) NH-Y,-( CH2) c CH2 NHCONH2 or-(CH2) dCH (R7) NR9R10; a is 1, 2 or 3; c is 1, 2 or 3; d is 0 or 1; R7 is fluorene or methyl; R9 is alkyl; R1 () is fluorene, q-Cw alkyl or amine protecting group; Y is fluorene, CN or N02; Q is -B (OH) 2, pinanediol dihydroxyborane ester, dicyclohexyl-i, i , -Diol dibasic firing S purpose or 1,2-dicyclohexyl-ethyl 4,2-diol dibasic firing ester; X is RAC (= 0)-, RANHC (where, ras ( = 〇) 2 "ra0C (= 0) ... rasc (Wa or RA; RA is substituted by r2G (VCm); C2_C2Q alkenyl substituted by R2G as appropriate; cvc2G alkynyl substituted by r2G as appropriate; Optionally a carbocyclic group substituted with 1-5 # 1 R21; or 95014 -33, 200529810 optionally a heterocarbocyclic group substituted with 1-5 R2 1; R2G is selected from the group consisting of:

_CN, i group, haloalkyl ... CrC4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C02H, -c (= o) co2h, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2, -OH, -SH, -NH2, -NH (alkyl), N (alkyl) 2, _NHC (= 0) NH2, · NHCpCOR2 ", -NHC (= O) OR20a, -OR20a, -SR20a, -S (= 〇) R20a, _s (= O) 2R20a, -S (= O) 2-NHR20a, -SC (= 0) R2 ° a , -C (= 0) R2Ga, _c (= 0) NHR2 ° a, -C (= O) O-R20a, -NHS (= 0) 2R2Qa, -NHR2 () b, phthalimide ,-(〇_alkyl) r, -〇-alkyl-OH,-(〇-alkyl) r_OH, -〇R20c, -SR20c, -O-ryl-R20c, -S-alkyl -R20e, -S (= O) -R20e, -S (= O) 2-R20c, -S (= O) 2-NHR20c--SC (= O) R20c > -C (= O) R20c > -C (= O) OR20c '-C (= 0) NHR2Ge, a carbocyclic group optionally substituted with 1-5 R21; and a heterocarbocyclic group optionally substituted with 1-5 R21; R ^ OaaCi- C ^ o alkyl, C2-C2o alkenyl or C2_C2o alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally one or more halo, Cl-C4 alkyl, aryl, heteroaryl Or -NHR20b * generation; 1 ^ 2 () 1) is an amine protecting group; R2Ge is a carbocyclic group optionally substituted by 1-5 R22; or optionally 1-5 R22 substituted heterocarbocyclyl; R21 is selected from the group consisting of: 〇1 < 20 alkyl, 〇2-. 2 () diluted group, 〇2-〇2〇 fast group, 〇1 < 2 () alkoxy group, Cl -C2 thiocarboxy group, -OH-CN, halo, haloalkyl, -NH2,- NH (alkyl), -N (alkyl), -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 0)-95014 -34- 200529810 alkyl, -c (= o) alkyl, -s (= 0) -alkyl, -s (= o) 2-alkyl, -S (o) -aryl, -S (= 〇) 2-aryl, Optionally a carbocyclic group substituted with 1-5 R22 and optionally a heterocarbocyclic group substituted with 1-5 R22; R22 is selected from the group consisting of: CVCw alkyl, C2-C10 alkenyl, C2-C10 alkynyl , Phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, alkyl-oc (= o)-, alkyl_C ( = 0)-, aryl-oc (= o)-, ^ alkyl-0C (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkane Radical -C (= 0) 0_, (alkyl-0) r_alkyl, HO- (alkyl_0) r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2 NS (= 0)-, and H2 NS (0) 2-; and r is 2, 3, 4, or 5 ; With the proviso that when x is rac (= 〇) _, ra is a C4-Ci5 straight chain alkyl group substituted by r2〇, and R20 is _CN, -C02H, -C (= O) O-R20a , -NHS (= 0) 2R2〇a, _NHC (= 〇) R2〇a, depending on R20b or o-phthalenediamine group; then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y , Where Υ Φ is Η, -CN, or -Ν02. In still further specific embodiments, the present invention provides a compound of formula ① or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form, wherein: R1 is c, c6 alkyl, C2-C6 dilute, C2 <: 6 fast radical or c3a cycloalkyl; r2 is -CH2 NH2 or -CH2 NR9 R1 〇; R is fluorene or Ci-C10 fluorenyl; H, Ci-C1 () alkyl, carbocyclic, hetero Carbocyclyl, Mm. Carbocyclyl_C (= Q) _, Heterocarbocycline · Ah), Carbocyclyl 95014 -35. 200529810

-CH)) ·, heterocarbocycloalkyl_c (= 0) ... Ci-Cio alkyl-s (= 〇) 2 ... carbocyclyl-S (= 0) 2-, heterocarbocyclyl- s (= 0) 2-, carbocycloalkyl-S (= 0) 2 ... heterocarbocycloalkyl-S (= 0) 2 ·, Ci-Cw alkyl-NHC (= 0)-, carbon Cyclo-NHC (= 0)-, heterocarbocyclyl_nhC (= 0)-, carbocyclyl alkyl group c (which, heterocarbocyclyl-NHC (= 0 >), q alkynyl- 〇C (= 0)-, carbocyclyl-〇C (= 〇)-, heterocarbocyclyl-0C (= 0) _, carbocyclyl-Oc (= 0) ... heterocarboalkane -0C (= 0)-or amine-protecting group; wherein Ri 0 is optionally substituted by 1, 2 or 3 R23; or, R9 forms a heterocarbocyclic group together with R1G and the N atom to which they are attached; Q is -B (OH) 2, -B (OR14) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains one which may be N, S or O heteroatom; R14 is H'q-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; X is RAC (= 0)-, RANHC (, _, RAS ( = 0) 2_, Ra〇c (= 〇) ... in RAS or RA; RA is CrCw alkyl substituted by R20 as appropriate; C2-C2G alkenyl substituted by R2G as appropriate; C substituted by R2 G as appropriate 〖-C〗 Fast radicals; carbocyclic radicals optionally substituted with 1-5 R21; or heterocarbocyclic radicals optionally substituted with 1-5 R21; R2 () is selected from the group consisting of: -CN, halo, haloalkyl -, Alkyl, c2-c4 alkenyl, c2_c4 alkynyl, -C02H, -C (= 0) C02H, -c (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2, -OH, -SH, _cis2, _NH (alkyl), -36- 95014 200529810

-N (alkyl) 2, -NHC (= 0) NH2, -NHC (= O) R20a, -NHC (= O) 〇R20a, -OR20a, -SR20a, -S (= O) R20a, -S ( = O) 2R20a, -S (= O) 2-NHR20a, _SC (= 0) R2〇a, -C (= O) R20a, -C (= O) NHR20a, -C (= O) O-R20a, -NHS (= O) 2R20a, -NHR20b, phthalimide,-(〇_alkyl) r, _〇_alkyl_OH, _ (0 alkyl) plant 〇11, -〇1120 . , Name 112 () (:, _〇-alkyl-R20c, alkyl-R20c, -S (= 0) -R2Gc, -S (= O) 2-R20c, -S (= O) 2-NHR20c ^ -SC (= O) R20c '-C (= O) R20c ^ -C (= O) OR20c' -C (K)) NHR2Ge, a carbocyclic group substituted with 1-5 R2 1 as appropriate; and as appropriate Heterocarbocyclic groups substituted with 1-5 R21; R2G a is Ci-C2o alkyl, C2-C2o or C2-C2o alkynyl; wherein the alkyl, alkenyl or alkynyl group is Case is substituted by one or more halo, Ci -C4 alkyl, aryl, heteroaryl or -NHR2Gb; R2 () b is an amine protecting group; R2Ge is a carbocyclic ring substituted by 1-5 R22 as appropriate Or a hetero carbocyclic group optionally substituted with 1-5 R22; R21 is selected from the group consisting of:

Ci-C2o alkyl, C2-C2o alkenyl, C2-C2Q alkynyl, CVC20 alkoxy, Ci (2othioalkoxy, -0H_CN, halo, haloalkyl, -NH2, -NH (Carbonyl), -N (Carbonyl) 2, -NHC (= 0) 0-Alkyl, _NHC (= 0) Carbonyl, -C (= 0) 0-Alkyl, -C (O) alkyl , -S (= 0) -alkyl, -s (= 0) 2-alkyl, -s (= 0) -aryl, -S (= 0) 2-aryl, optionally 5 R2 2 Substituted carbocyclyl and heterocarbocyclyl substituted with 1-5 R2 2 as appropriate; R22 is selected from the group consisting of: CVCk alkyl, C2-C10 alkenyl, c2-C10 alkynyl, phenyl, halo, 95014- 37- 200529810 haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, alkyl-oc (= o)-, alkyl-c (= 0)- , Aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (Carbonyl-0) r-Organyl, HO- (Carbonyl-0) r-Carbonyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl -S (= 0)-, alkyl-S (= 0) 2-, H2NS (= 0)-, and H2NS (= 0) 2-; R23 is selected from the group consisting of:

(VC6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, F, Cl, Br, I, haloalkyl, -NH2, -NHR23a, -N (R23a) 2, -N3, -N02, -CN,-- CNO, -CNS, -C (= 0) 0R23a, -C (= 0) R23a, -0C (= 0) R23a, -N (R2 3 a) C (= 0) R2 3 a, -C (= 0 ) N (R2 3 a) 2, ureido, -OR2 3 a, -SR2 3 a, -S (= 0) 2-(C 「C6 alkyl）, _s (= 0) 2 -aryl and -s (= 0) 2 -N (R2 3 a) 2;! ^ 23 " is 11 or CrC6 alkyl; or, two R23a may be combined with the N atom to which they are attached to form a 5 to 7 member A ring group; and r is 2, 3, 4 or 5. In still further specific embodiments, the present invention provides a compound of formula ① or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein : R is Ci-C8 alkyl, C2-C8 alkenyl, c2-C8 alkynyl or C3-C7 cycloalkyl; R2 is Η; Q is hepta (OH) 2, -B (ORi4) 2 or cyclic di Hydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains a hetero atom which may be N, S or 0; RU is H'q-C4 alkyl, naphthenic Radical, cycloalkylalkyl, aryl or aralkyl; 95014 • 38- 200529810 X is RaC (= 0)-, RaN HC (= 0)-, RaS (= 0) 2-, RA〇C (= 〇)-, RaSC (= 0)-, or ra; RA is Ci-C ^ o alkyl substituted by R2G as appropriate; as C2-c2G alkenyl substituted by R2G; c2-c2G alkynyl substituted by r2G as appropriate; carbocyclyl substituted by 1-5 R22 if appropriate; or hetero substituted by 1-5 R2 2 if appropriate Carbocyclyl; R2. Is selected from the group consisting of: -OR20a, -SR20a, -S (= O) R20a, -S (= O) 2R20a, -S (= O) 2-NHR20a, -SC (= O) R20a, -C (= O) R20a, -C (= O) NHR20a, -C (= O) O-R20a, o-benzyl dimethyl imine,-(0-alkyl) r, -0-carbon -OH,-(0-alkyl) r-OH, -OR2 () c, -SR2Gc, -0-alkyl-R2 () c, alkyl-R20c, -S (= 〇) -R20c,- S (= O) 2-R20c, -S (= O) 2-NHR20c, -SC (= O) R20c, -C (= 〇) R20c, _C (= O) OR20c, -C (= O) NHR20c, A carbocyclic group optionally substituted with 1-5 R22; and a heterocarbocyclic group substituted with 1-5 R22 as appropriate; and R oa is C! _C2o alkyl, C2-C2o alkenyl, or c2 -C2 alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally substituted by one or more halo, CrC4 alkyl, aryl, heteroaryl or -NHR2Gb; R2Ge is optionally 1- 5 R22 substituted carbocyclic groups; Or optionally a heterocarbocyclic group substituted with 1-5 R22; R22 is selected from the group consisting of:

Cl-Cl 0 alkyl, C2-Cl 0 fine, C2-Cl 0 fast, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamine 95014 • 39- 200529810 group, weidyl group, alkynyl group_ ° C (= 0), alkynyl group-0 (== 0)-, aryl_oc (= o), alkyl-0C (= 0) NH-, aryl-OC (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (alkyl-0) r-alkyl, HO- (Alkyl-0) r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2- , H2 NS (= 0)-and H2 NS (= 0) 2-; and r is 2, 3, 4, 5, 6, 7, 8, 9 or 10. In a still further specific embodiment: X is RAC (= 0)-, RANHC (= 0)-, RAS (0) 2-, or RA; RA is a CrC14 alkyl group optionally substituted by R20; R2G is-( 0-alkyl) r-OH or-(0-alkyl) r- (0-alkyl); and r is 1, 2, 3, 4 or 5. In a further specific embodiment, the 0-alkyl is fluorenyl, ethoxy, or propoxy. In still further specific embodiments, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is 2-propyl; R2 is -ch2ch2ch2nhc (= nh) nh-no2, -ch2ch2ch2nhc (= o) ^^ -ch (ch3) oh, -ch2conh2, -ch2nh2 or -ch2nr9r10; call R9 to be Η; R is methyl-C (= 0)-, ethyl- C (= 0)-, propyl-C (= 0) _, butyl-C (= 0)-, pentyl-C (= 0)-, 2- (ethoxycarbonyl) ethyl_c (= 0) _, 4-fluorenyl-benzyl-C (= 0)-, cyclopropyl-c (= 0)-, 4-fluorophenyl_C (= 0) _, 4-H2NS02-phenyl- C (= 0) _, 4-H3 CS02 -phenyl ((: (= 0)-, 4-phenyl-phenyl · (: (= 0)-, monomethoxy-fluorenyl-C (= 〇)-, 3-exo-stilbyl-C (= 0)-, 2- (transyl) -physin-3-yl-C (= 0)-, 6- (morpholinyl) -pyridine Each group -C (= 0)-, 2-0 than pyridin-4-yl) farazol-4-yl-C (= 〇)-, 2-pyridyl_C (= 0)-, 2,5 -Difluorenyl- 95014 -40- 200529810 pyrazolyl-C (= 0)-, N-methyl-2-pyrrolyl-C (= 0)-, 2-tetrahydropyrrolyl_C (= 0 > , 2-thiophenyl_C (= 0) _, 5-isooroxazolyl-C (= 0)-, 4- (tetrazol-5-yl) phenyl-C (= 0)-, ( 5-tetrazolyl) CH2_C (= 0)-, N-H3CS02 -Hexahydropyridyl-C (= 0)-, butyl_0C (= 0) _, (benzyl) -0C (= 0) _, (9-thylmethyl) -0C (= 0)- , Pentyl-NHC (= 0)-, propyl-NHC (= 0)-, phenyl-NHC (= 0)-, 4-methyl · phenyl-NHC (= 0) _, methyl-S (= 0) 2-, 4-Gaphthyl-S (= 0) 2_, 4-Hexyl-phenyl-S (== 0) 2, 1-Methyl_ormidol-4_yl-S (= 0) 2-, 2-thiophenyl-S (= 0) 2-, (4-methyl-phenyl) -NHC (= 0) NH-S (= 0) 2-and (4-methyl -Phenyl) -S (= 0) 2 NHC (= 0)-, or R9 forms a pyrrolyl or pyrazolyl together with R1G and the N atom to which they are attached; Q is -B (OH) 2 Pinanediol dihydroxyborane ester, dicyclohexyl-1, Γ-diol dihydroxyborane ester, or 1,2-dicyclohexylethane-1,2-diol dihydroxyborane ester; X is RaC (= 0)-, RaNHC (= 〇)-, rAs (= 〇) 2-, or raoc (= o)-; RA is CH3-, C2H5-, C3H7-, C4H9-, C5Hn-, C6H13-, C7H15- , C8H17-, C9H49-, C10H21-, C11H23-, C12H25-, C13H27-, Austenyl-, dicycloheptyl-, C3-alkyl substituted with R2G; C2-l0 alkenyl substituted with R2G ; Cyclopropyl substituted with 0-3 R21; Cyclopentyl substituted with 0-2 R21; Ring substituted with 0-2 R21 Benzyl group substituted by 0-3 R21; 95014 -41-200529810 Naphthyl group substituted by 0-2 R21; p-pyhyl substituted by 0-1 R2 1; 0-1 R2 1 Substituted quinolinyl; imidazolyl substituted with (M R2 1; tetrahydrofuranyl substituted with 0-1 R2 1; ketooxazolidinyl substituted with 0-1 R2 1; 0-1 R2 1 substituted benzopyrazolyl;

Pyrazolyl substituted with 0-2 R21; furanyl substituted with 0-2 R2 1; tetrahydropyrrolyl substituted with 0_1 R2 1; hexahydropyridyl substituted with (M R2 1); 0-1 R2 1 substituted hexahydro P-pyridyl; or p-1 fluorenyl substituted with 0-1 R2 1; R2Q is selected from the group consisting of: hydroxy-, methoxy-, ethoxy, propoxy Yl-, butoxy-, pentyl-, hexyl-, heptyl-, octyl-, ethoxyethoxy-, methoxyethoxyethoxy-, methyl- s_, ethyl-S-, octyl-s-, methyl-C (= 0) S-, (acetamido) methyl each, amino, methylamino-, diamido-, -C (= 0)-, phenyl-c (= 0)-, (H3CS02) phenyl-C (= 0)-, thiophenyl-c (= 0)-, methyl-〇c (= 0)-, ethyl-0C (= 0)-, butyl-〇C (= 0) NH-, fluorenyl-CK)) NH ·, methoxyethoxymethyl-C (= 0) NH -, H2NC (= 0)-, methyl-NHC (= 0)-, ethyl-NHC (= 0)-, propyl-NHC (= 0)-, phenyl-NHC (= 0)-, H2NC (= 0) NH-, # H2NS (= 0) 2-, octyl_S (= 0) 2-, phenyl-SH)) 2-, fluorenylphenyl 95014 -42- 200529810 -S (= 0 ) 2 ", thiophenyl-S (= 0) 2-, cyclofluorenyl-, cyclohexyl-, cycloheptyl-, gold steel Alkyl-, dicycloheptyl-, cyclopentenyl-, phenyl-, methoxy-phenyl-, methyl-phenyl-, difluorenyl-phenyl-, ethyl-phenyl-, Propyl-phenyl-, butyl-phenyl-, gasophenyl-, difluoro-phenyl-, chlorophenyl-, bromophenyl-, iodophenyl-, dimethylamino-phenyl-, Cyclohexyloxy-, 2-isopropyl-5-methyl-cyclohexyloxy ·, fluorenyl-, methoxynaphthyl-, fluorenyl-, phenoxy-, (methyl-phenyl ) Oxy-, (ethyl-phenyl) oxy-, (propyl-phenyl) oxy ·, (butyl-phenyl) oxy-, (fluoroφphenyl) oxy-, (chloro Phenyl) oxy-, (bromophenyl) oxy-, phenyl each, fluorenyl-S-, (fluorenyl-phenyl) fluorenyl-S-, 0 dense stilbyl-S-, hexaazapyridine α-Amino_, N-fluorenyl-hexakis ^ A-σ-Amine-, n-propyl-Hydratamine, σ-Amine, phthalimide-, thiophenyl-, methyl-thiophenyl -, Wei 11 syl-, succinyl-, tetrasigma sti- -, Ethyl-, propyl, butyl, fluorenyl-, hexyl-, heptyl-, ethyl Propyl-, propyl-, butyl-, phenyl-, lactyl-, ethoxy, propoxy-, phenoxy-, fluoro-, chloro-, molyl-, methyl-C (= 0) -, Butyl-0C (= 0)-, Butyl-0C (= 0) NH-, Phenyl-, Phenoxyphenyl-, Phenyl-, Phenyl-, Mophenyl-, Say σ Each base-and? Than σ fixed base. It should be understood that certain features of the present invention have been described in the context of individual specific embodiments for clarity, and they may also be provided in combination in a single specific embodiment. Conversely, various features of the present invention are described in the context of a single specific embodiment for the sake of brevity, and they may be provided individually or in any suitable combination of 95014-43-200529810. As used herein, the term "dihydroxyborane" refers to a compound containing a partial group b (0h) 2. In some embodiments, a dibasic compound can be used by the dibasic compound The dehydration of several groups of groups forms oligomeric quinones. For example, Snyder et al., "/ Zucchini" 19S8, 80, 361 [Report oligomeric aryldihydroxyborane. Therefore, unless stated otherwise, the chemical formula of "dihydroxyboron" or a group containing -B㈣2 is intended to cover free ^ dihydroxyborane, oligomeric anhydrides, including but not limited to dimer, trimer Polymer, tetramer and mixtures thereof. In response to "dihydroxyborane anhydride" or "dihydroxyborane anhydride" used herein, it refers to a compound by combining two or more molecules The group formed by the loss of one or more water molecules, when in contact with water, 'can make the compound of the two warp side field hydration to release the free state of the two warp base compound. In some specific In embodiments, the structure of the two warp needles may contain two, three, four or more two warp warrior units and may have a cyclic or linear configuration. In some specific embodiments, the two springs are reduced to iMb compounds. It essentially exists in the form of mono-recruitment polymerization; however, the two-class radicals also include mixtures of different re-acquired dimorphic radicals, as well as free-state dihydroxyborane. Non-limiting examples include compounds of formula (π) and ㈣, where G is a moiety of formula (IV), and t is 0 to 10, or !, 2, 3, or 4 0095014 -44 · 200529810

In some embodiments, at least about 80% of the two compounds present in the two-pass base burning anhydride compound are present in the form of a single polymerized anhydride. In a further specific embodiment, at least about 85, about 90, about 95, or about 99% of two of the dihydroxyborane anhydrides present in the dihydroxyborane anhydride are present in the form of a single oligomeric field. In some embodiments, the dihydroxyborane anhydride compound essentially comprises a single polymeric dihydroxyborane anhydride. In yet a further specific embodiment, the dihydroxyborane anhydride compound comprises a single polymerized dihydroxyborane anhydride. In a further specific embodiment, the dihydroxyborane anhydride compound contains a boroxine of formula (III), where t is 1. Dihydroxyborane anhydride compounds can be prepared from their corresponding dihydroxyborane compounds' in a manner that is exposed to dehydration conditions, including, for example, crystallization, 95014 -45- 200529810 lyophilization, exposure to heat and / or exposure to dryness Agent. Some suitable crystallization solvents include ethyl acetate, digasmethane, hexane, ether, benzene, acetonitrile, ethanol, and mixtures thereof. As used herein, the terms "dihydroxy stilbene ester" or "dihydroxyboronate π" refer to an ester derivative of a dihydroxyborane compound. As used herein, π cyclic dihydroxyborane ester "is It means that the stable cyclic dimer group of the general formula _B (0R) (0R) is partially fired, in which two R substituents are linked together, and Φ forms a cyclic partial group (for example, 3_ To 10-membered cycloalkyl), optionally further substituted with one or more substituents, or fused with one or more other carbocyclyl or heterocarbocyclyl (shares at least one bond). The cyclic dihydroxyborane ester may contain 2 to 20 carbon atoms and optionally contains a hetero atom which may be N, s or 0. % -Based borosulfuric esters are known in the art. Examples of cyclic dibasic side alkyl esters include, but are not limited to, pinanediol dihydroxyborane ester, pinacol dihydroxyborane ester, 1,2-ethanediol dihydroxyborane ester, 13- Glycolol side-burner ester, 1,2-propanediol diammonium borohydride, 2,3-butanediol rudimentylboronate, 1,1,2,2-tetramethylethyl Burnt diol dibasic stilbene ester, I. Diisopropyl ethyl diol dibasic side burned ester, 5,6-decyl diol dibasic sparpentyl ester, 1,2-dicyclohexyl Ethanediol dihydroxyborane ester, dicyclohexyl fluorene glycol, diethanolamine dihydroxyborane ester, and 1,2-diphenyl-1,2-ethanediol dihydroxyborane ester. In some specific embodiments, the “π-cyclic dihydroxyborane ester” has the formula (n_a): 95014 -46- 200529810

(Π-a) where: D is absent, 0, s, NR16 or CR15 e Ri 5 f; R, Ri5b, Ri5C, R15d, R15e, Ri5f are each independently H, A ·. . Alkyl, qc: 7 cycloalkyl, aryl, or heteroaryl, wherein the alkyl group, C3-c1 () cycloalkyl, aryl, or heteroaryl, is optionally Halo, CVQ alkyl, Cl_4 alkyl, alkoxy, 0H, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; or Rh is connected to R ^ b and others The C atoms together form a q-Cw cycloalkyl or a 3- to 10-membered heterocycloalkyl, each of which is optionally a halo, 2, 3, or 4 halo, alkyl, Cl_c4 alkoxy, Ci_Q_alkane Oxy, 0h, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; or R15c and Riw and the pyrene atom to which they are attached together to form a C3_Cio cycloalkyl or 3- to 10-membered heterocycloalkyl, each optionally halved, 2, 3, or 4 halo, CVC4 alkyl, CVC4 alkoxy, Cl_c4_alkoxy, 0H, amine, alkylamino, dialkylamine Group, aryl or heteroaryl substitution; or Rl 5b and Rl 5e and the C atom to which they are attached and the D moiety inserted together to form an aryl, heteroaryl, C3_Cio cycloalkyl or 3_ To 10-membered heterocyclic alkyl groups, each optionally i, 2, 3 or 4 halo, CrQ alkyl, Ci-C4 Oxy, (^-(: 4ΐ | alkoxy, 0H, amine, alkylamino, dialkylamino, 95014-47- 200529810 aryl or heteroaryl substitution; R16 is fluorene or CrC6 alkyl; And p and q are each independently i, 2 or 3. In some specific embodiments, in some specific embodiments, in some specific embodiments, in some specific embodiments, and in some specific embodiments, u horse does not exist. D is NRi 6 0 D is NH 〇 D is CH2 〇

R and Han 151) and their connected sons' together form C3-Cl. Cycloalkyl or 3- to 10-membered heterocycloalkyl: 1,2,3, or 4 octyl groups,% octyl groups, A, pentyloxy, OH, amine, Amine, diamine, aryl, or oxo substitution; and the ruler is connected to Han and others. original? Together to form a cycloalkyl group or a 3 · to ΐ〇 · Μ heterocyclic group, each of which is optionally 1, 2, ..., ^ groups, alkyl groups, Cl-C4 alkyloxy groups, Ci_C4 alkyloxy groups, η , Amino ', alkylamino, dialkylamino, aryl or heteroaryl. In some specific embodiments, Rl5a # Rl5b and the C atom to which they are connected together form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl group; and R⑴ is connected to W and to them As atoms, it forms cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. In some embodiments, D is absent, and 111513 and 1115. Together with the C-ortho + to which they are connected, an aryl group and a heteroaryl group are formed. . Cycloalkyl or 3- to 10-membered heterocycloalkyl, each optionally being i, 2, 3, or 4; Ci_C4 alkyl, Q-Q alkoxy, q-C4- alkoxy, OH , Amino, alkylamino, dialkylamino, aryl or heteroaryl. 95014 -48- 200529810 In some specific embodiments, 0 is absent, and R "b is connected to R15C and the C atom to which they are connected. _. Jba rL ^^ is formed into (Vc1 () cycloalkyl, depending on The case is substituted with one, two, three, or four functional groups: '% alkyl,% alkoxy, fluorenyl alkoxy, OH alkylamine, dimorphamine, aryl, or heteroaryl. Some specific In the examples, 0 is absent, and r15J ^ r15c and the kappa atom to which they are connected form a c3c1G ring county, optionally substituted with 2, 3, or 4 halo groups or 0: <4 alkyl groups.

In some embodiments, D is absent, and r151 ^ r15c and their connected are formed by +. Bicyclic cycloalkyl, optionally substituted with 2, 3 or 4 halo or q-C4 alkyl. In some embodiments, P and q are each 1. In some embodiments, at least one of R15a, R15b, R15c, and R15d is not tritium.

Other examples of &quot; cyclic dihydroxyborane esters &quot; as defined herein include dibasic burned esters having the following structure:

Ring or substituted or where: W is a substituted or unsubstituted C4-C1G cycloalkyl95014 -49- 200529810 unsubstituted benzene ring; w1 is independently a substituted or unsubstituted 03-06 cycloalkyl ring. The groups R15a, R15b, R15c, R15d, R15e, R15f P and q are all defined as provided above. The term "alkyl" or "alkylene" as used herein is intended to refer to a saturated or branched saturated nicotinyl group. Examples of alkyl groups include methyl (Me), ethyl (Et), Propyl (eg n-propyl and isopropyl), butyl (eg n-butyl, isobutyl, second-butyl, third-butyl), pentyl (eg n-pentyl, iso (Pentyl group, neopentyl), etc. The alkyl group may contain 1 to about 20, 2 to about 20, 1 to about 10, 1 to about 8, 1 to about 6, 1 to about 4, or 1 to about 3 Carbon atom. A "diluted group" as used herein refers to an alkyl group having one or more carbon · carbon double bonds. Examples of alkenyl include vinyl, propenyl, butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl, and the like. As used herein, "alkynyl" refers to an alkyl group having one or more carbon-carbon reference bonds. Examples of fastyl include ethynyl, propynyl, butynyl, pentynyl and the like. • As used herein, haloalkyl, means an alkyl having one or more halogen substituents. Examples of haloalkyl include CF3, C2F5, CHF2, CC13, CHC12, QCl5 and the like. An alkyl group in which all hydrogen atoms are replaced by halogen atoms can be referred to as 'fperS alkyl'. Examples of per-alkyl include CF3 and c2f5. As used herein, a "carbocyclyl" is a group of cyclic hydrocarbon moieties that are saturated (meaning that they do not contain a double or reference bond) or unsaturated (that is, that contain one or more double or reference bonds). Carbocyclyl can be mono- or polycyclic. Examples of carbocyclyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, 1,3-cyclopentadienyl, cyclohexenyl, n-boxyl, n- Pingyl, n-carbyl, gold steel alkyl, 95014-50-50200529810 phenyl and so on. Carbocyclic groups can be alkyl "). In-*, it is solid: such as * group") or non-aromatic (for example, "rings up to 7 / = carbocyclic groups can have 3 to 3, 3" "Mao group" refers to an aromatic carbocyclic group, which includes a monocyclic ring such as phenyl, anthracenyl, phenanthryl ...: 成; 的: atomic-. Some specific implementation ...

As used herein, "cycloalkyl" means ^ ^ # 〒? Japanese-African private slaves, including coated alkyl, alkenyl and alkynyl. Examples of cyclic earth J dagger double or more ring-shaped ring-containing alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentane, cyclopentenyl, cyclohexenyl, cyclohexane , Cycloheptadienyl di-n-primary, n-pinyl, n-carbyl, auryl and the like. In the definition of cycloalkyl group) to the ring of the aromatic ring of the alkynyl ring, the scoring group of 10,000 ranks, such as cyclopentane (hydroindenyl), cyclohexane (tetrahydronaphthyl) And other benzo derivatives. In some specific implementations, it also includes a &quot; or more fused (meaning it has a common bond with it, the cycloalkyl group may have 3, 4, 5, 6, or 7 carbon atoms that can form a ring In some implementations, the fluorenyl group may have 0, 13 and 2 bonds that can form a double or a reference ring. As used herein, a "heterocarbocyclic group" may be a saturated or unsaturated carbocyclic group. Where one or more carbocyclyl carbon atoms that can form a ring are replaced by a heteroatom such as 0, s, or N. A heterocarbocyclyl can be aromatic (eg, heteroarylπ) or non-aromatic Family (eg "heterocycloalkyl"). Heterocarbocyclyl may correspond to hydrogenated and partially hydrogenated heteroaryl. Heterocarbocyclyl may contain from about 1 to about 20, about 2 in addition to at least one heteroatom. To about 10 or about 2 to about 7 carbon atoms, and may be linked via a carbon 95014-51-200529810 atom or heteroatom. Examples of heterocarbocyclic groups include morpholinyl, thiomorpholinyl, hexahydro Pyryl, tetrahydrofuryl, tetrahydropyrimyl, 2,3-dihydrobenzofuranyl, 1,3-benzodioxolene, benzodiazepine, Hydropyridyl, tetrahydropyrrolyl, isotetrahydropyrazolyl, isopyrimidyl, tetrahydropyrazolyl, tetrahydrooxazolyl, thiazolyl, tetrahydroimidazolyl, etc., as used herein " "Heteroaryl" is an aromatic heterocarbocyclic group and includes monocyclic and polycyclic aromatic hydrocarbons having at least one heteroatom ring member such as sulfur, oxygen, or nitrogen. Heteroaryl systems include, but are not limited to Pyridinyl, pyrimidinyl, pyrimidinyl, talhuyl, trisyl, cylanyl, benzyl, isoprenyl "sedenyl, imidazolyl, pyrazolyl, kolodol, pyrrolyl, pyridine Oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, trisialyl, tetrasalyl, benzoyl, oxal, dioxanyl, isosalyl , Benzofluorenyl, purinyl, carbazolyl, benzimidazolyl, etc. In some embodiments, heteroaryl may have 3 to about 20 carbon atoms that can form a ring; In specific embodiments, it is about 3 to about 12 carbon atoms that can form a ring. II In some embodiments, the heteroaryl group has from about 4, to about 3, or ^ to heteroatoms As used herein, &quot; heterocyclic alkyl &quot; refers to a non-aromatic heterocarbocyclic group, including cyclized morpho groups, dilute groups, and alkynyl groups, in which-or more carbon atoms that can form a ring are For example, the replacement of heteroatoms of 0 and MS atoms. Carbon and heteroatoms that can form a ring such as S and N 'can be further oxidized in the heterocyclic group moiety. May carry—or two keto groups or sulfide moieties (for example, &gt; C =., Example, AH, etc.). In the definition of heterocarbon group, it also includes having one or more fused groups (This means that Panpan 95014 -52- 200529810 has a part of the group of the aromatic ring with a common bond 1_ F known, such as 郇 本 一 甲 醯 imino group, Guan — 'ding, a methyl group Imino, diamido pyromelite, phthalic acid, and benzo derivatives of saturated heterocycles, such as indole and isoindole groups. In these two embodiments, the heterocycloalkyl group has 3 to about 20 ring-forming atoms. In some embodiments, the heterocycloalkane a 5 6 or 7 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 0, //, 0, 1 or 2 bonds which can form a double or a reference ring. As used herein, the "halomeric" formulas include fluoro, fluoro, bromo, and acryl. "Alkyl" which is used in this document and 4t a ^ succinic group. Examples of alkoxy include methoxy6oxy, propoxy (such as n-propoxy and isopropoxy), tertiary-butoxy, etc. In some embodiments, alkoxy has 1 to 2〇, ^ 12 'UH6' 1 to 4 or 丨 to 3 carbon atoms. As used herein, &quot; alkoxyalkoxy &quot; refers to -0-sinyl · 0xyl. Used in this text In other words, "thioalkoxy" means an alkoxy group in which 0 atom is replaced by an s atom. "Aryloxy" as used herein means an aryl group. An example of aryloxy is phenoxy. As used herein, "thioaryloxy" refers to an aryloxy group in which 0 atom is replaced by an s atom. "Aralkyl" as used herein refers to an alkyl moiety group substituted with an aryl group. Examples of aralkyl include benzyl and fluorenylmethyl. In some embodiments, the aryl group has 7 to 11 carbon atoms. As used herein, amine group π refers to an N-NH2 group. "Baking amino" refers to an amine group substituted with an alkyl group of 95014 * 53-200529810, and "dialkylamino" refers to an amine group substituted with two alkyl groups. Conversely, "amino alkyl group π" refers to Amine-substituted alkyl. As used herein, '' carbonyl 'means> c = 0. As used herein, "carboxyπ or" fluorenyl "means -COOH. As used herein, &apos; &apos; Cyclo &apos; &apos; refers to -OH. "Mercapto" as used herein refers to -SH. Pi ureido as used herein refers to · ΝΗ (^ 〇ΝΗ2. "Sulfinyl" as used herein refers to> so. As used herein, &quot; mercapto, &quot; means &gt; S〇2. &Quot; oxy &quot;, as used herein, means, 〇_. The above chemical terms may be combined to refer to a moiety containing a combination of chemical groups. In general, this combination of terms is read so that the enumerated terms are made explicit as a substitute for the next term. For example, &quot; alkylcarbonylalkenyl M refers to an alkenyl group substituted with a carbonyl group , Which in turn is substituted by an alkyl group. The following terms can also exemplify such a combination. As used herein, "carbocyclyl alkyl" refers to an alkyl moiety partially substituted by a carbocyclic group. Carbocyclic Examples of arylalkyl include "aralkyl" (alkyl substituted with aryl) and π cycloalkylalkyl "(alkyl substituted with cycloalkyl). As used herein, carbocyclene "Alkyl" means an alkenyl moiety group substituted with a carbocyclyl group. Examples of carbocyclyl alkenyl groups include "arylalkenyl with aryl Instead alkenyl group) and π cycloalkylalkenyl "(alkenyl substituted by the cycloalkyl group). As used herein, "carbocyclylalkynyl" refers to an alkynyl moiety substituted with a carbocyclyl. Examples of carbocyclylalkynyl include, aralkynyl, (alkynyl substituted with aryl), and "cycloalkylalkynyl" (alkynyl substituted with cycloalkyl). 95014 -54- 200529810 = "Heterocarbocyclyl" as used herein refers to a moiety of a carbocyclyl substituted with a heterocarbocyclyl. Examples of heterocarbocyclyl include, heteroaryl "(Cycloyl substituted with heterosquaryl) and, heterocyclyl" (Cycloalkyl substituted with heterocyclyl) "" heterocarbocycloalkenyl "as used herein refers to the Heterocarbocyclic substituted dilute moieties. Examples of heterocarbocyclyl include, fluorenyl dilute radical (diluted radical substituted with heteroaryl) and "heterocycloalkylenyl" (0 alkenyl substituted by heterocycloalkyl). As used herein, "heterocarboalkynyl" refers to a group that is taken by a heterocarbocyclyl group. Examples of carbocyclyl groups include "heteroarylalkynyl" ("heteroaryl" Alkynyl substituted with alkynyl) and "heterocycloalkynylalkyl" (alkynyl substituted with heterocycloalkyl). As used herein, the term "protecting group" refers to a group that can be optionally attached to, for example, a hydroxyl group, an amino group And functional groups that remove and remove carboxyl functional groups. Protecting groups are usually introduced into compounds to make such functional groups inert to the chemical reaction conditions to which the compound is exposed. Any of a variety of protecting groups One kind can be used together with the present invention. The protecting group of the amine group may be referred to as, the protecting group of the amine group, and the protecting group of the guanidine group may be referred to as the guanidino group. Protective group ". The amine group and the guanidino protecting group may have a chemical formula of aryl-S02-, alkyl-S02-, aryl-c (= 0)-, aralkyl-c (= 0), and alkyl-c ( = 0)-, aryl-0C (= 0)-, aralkyl-〇c (= 〇) _, alkyl_〇c (= 〇) _, aryl-NHC (= 0)-, alkyl -NHC (= 0)-, etc., wherein the alkyl group, aryl group, and aralkyl group may be substituted or unsubstituted. Examples of amine and guanidino protecting groups may also include tertiary-butoxycarbonyl (BOC), fluorenylmethoxycarbonyl (Fmoc), fluorenyloxycarbonyl (Cbz), and phthalates 95014 -55- 200529810

Other representative protecting groups can be found in XW. Green and PGM · Wuts, Containing the Protection of Shame, 3rd Edition, Wiley & Sons, New York (1999), which is provided in its entirety and provided herein. reference. As used herein, "substituted" means that at least one hydrogen atom of a chemical group is replaced with a non-hydrogen moiety. Examples of substituents include F, α, order, 1, qQ alkyl, CrC6 alkenyl, CrC6, alkynyl, haloalkyl, Nrerf, N3, N02, CN, CNO, CNS, C (= 0) 0RE, REC 〇, REC (= 〇) 〇, RECONRE, RERFNC0, ureido, 〇rE, SRE, S (V alkyl, S (v aryl and scvnrerf, where the perch and 栌 are independently 11 or (:: 1_ (: 6 alkyl, or 舻 and 妒 can be combined with the nitrogen to which they are attached to form a 5 to 7 member%, such as tetrahydropyrrolyl, hexahydropyridyl, morpholinyl, hexahydropyridine And N-methyl hexahydropyridinyl group. When the chemical group herein is "substituted," the sundial 'may have a substitution of the highest complete valence, provided that the compound formed is a stable compound or a stable structure ; For example, methyl can be substituted with 1, 2 or 3 substituents, methylene can be substituted with 1 or 2 substituents, phenyl can be substituted with 1, 2, 3, 4 or 5 substituents, etc. 95014 -56- 200529810 "Leaving group π" as used herein refers to any group that can be replaced by a nucleophilic group upon nucleophilic substitution. Examples of leaving groups include halo groups (F, Cl, Br, I) , Hydroxyl, burn Radical, sulfenyl, thioalkoxy, trifluoromethylsulfonate, alkylsulfanyl, substituted alkylsulfonate, arylsulfonate, substituted arylsulfonate, heterocyclicsulfonate or Trichloroacetamidate. Representative examples include p- (2,4-dinitroaniline) benzenesulfonate, benzenesulfonate, methanesulfonate, p-methylbenzenesulfonate, p-bromo Benzenesulfonate, trisaminoacetamidoimidate, fluorenyloxy, 2,2,2-trifluoroethanesulfonate, imidazoliumsulfonyl, and 2,4,6-trichlorophenyl. Used in this document The "stable compound" or "stable structure" refers to a compound that is sufficiently robust to remain in the reaction mixture, isolated to useful purity, and is preferably a compound that can be formulated into an effective therapeutic agent. The present invention is directed only to stable compounds The compounds described herein may be asymmetric (eg having one or more stereocenters). Unless otherwise indicated, all stereoisomers are intended, such as paraisomers and diastereomers. Compounds of the invention containing asymmetrically substituted carbon atoms may be optically active or racemic The method for preparing an optically active form from an optically active starter f is known in the art, for example, by the resolution of a racemic mixture: many geometric isomers such as olefins, double bonds, etc. Among the compounds described in the above, and all such stable isomers are to be included in the present invention, the isomers are described, and two = combination: the cis and trans geometric forms are single Mixtures of isolated .isomers or separated isomers 95014 -57- 200529810 In addition to the above, the compounds described herein may have asymmetric centers that would cause a paraisomer of a compound of formula (I) Demonstrate superior biological activity over its relative isomers. Both types of amidine are considered to be part of the present invention. For example, the R2 substituent of a compound of formula (I) may exist in either S or R configuration. An example of the preferred configuration of the palm isomers of the present invention is a compound of formula (I-s) ...

It is not intended to be limited to this example. When required, separation of racemic materials can be achieved by methods known in the art. The compounds of the present invention may also include tautomeric forms, such as keto tautomers. Tautomeric forms can be in equilibrium, or can be locked into one form by appropriate substitution.

The compounds of the invention may also include all isotopes present in the intermediate or final compound: Isotopes include atoms with the same atomic order, but not [mass numbers. For example, the isotope system of hydrogen includes gas and deuterium. The term "pharmaceutically acceptable" is used herein to refer to 4 μ μ, and the mouth and / or dosage form, which is within the scope of safe and reliable medical judgment η, is applicable to humans and animals Tissue contact without undue, sexual, irritating, allergic response or other problems or complications, accompanied by a well-known benefit / risk ratio. The invention also includes pharmaceutically acceptable salts of the compounds described herein. 95014- 58- 200529810

"Pharmaceutically acceptable salt," as used herein, refers to the organism of the disclosed compound, wherein the parent compound is modified by converting the acid or moiety present to its salt form. Pharmaceutical Examples of acceptable salts include, but are not limited to, test residues such as mineral or organic acid salts of amines; acidic residues such as slow acid or organic salts, etc. The pharmaceutically acceptable sleep of the present invention includes the parent compound It is customary to use non-toxic salts or quaternary materials, which are self-explanatory = non-toxic inorganic or organic acids are formed. For example, such non-toxic salts include those derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, Sulfuric acid, amino acids, phosphoric acid and salts made from organic acids such as acetic acid, propionic acid, gallic acid, glycolic acid, stearic acid, lactic acid, lic acid, tartaric acid, citric acid, ascorbic acid, bis Acetic acid, maleic acid, maleic acid, phenylacetic acid, acetic acid, benzoic acid, salicylic acid, M, 2-acetoxybenzoic acid, fumaric acid, toluene Acid, formic acid, acetic acid, oxalic acid, Acetic acid, etc. The pharmaceutically acceptable salts of the present invention can be obtained from the parent compound containing basic or acidic moieties by conventional chemical methods.-Generally, such salts can be obtained by making these compounds It is prepared by reacting the free acid or base form with a stoichiometrically appropriate base or acid in water or in an organic solvent, or a mixture of the two; in general a 'non-aqueous medium' such as ether, acetic acid Ethyl, ethanol, 2-alcohol, or acetonitrile are more preferred. A list of suitable salts can be found in the postal review, Watson Review, 17th Edition, Mack Publishing Company, Easton, pa, 1985, p. 1418, and Science, 66, 2 (1977), the disclosure of each of which is hereby incorporated herein by reference. Synthesis 95014 -59- 200529810 The compounds of the present invention, including salts and solvates thereof, can be synthesized using known organic compounds. It can be synthesized according to any number of possible synthetic routes. The reaction for preparing the compounds of the present invention can be carried out in a suitable solvent, which can be easily selected by a person skilled in organic synthesis. The proper solvent is at the temperature at which the reaction is performed, meaning can A temperature ranging from the freezing temperature of the solvent to the boiling temperature of the solvent may be substantially non-reactive with the starting material (reactant), intermediate, or product. The specific reaction may be in one solvent or a mixture of more than one solvent According to the specific reaction steps, suitable solvents for the specific reaction steps can be selected. The preparation of the compounds of the present invention can involve the protection and removal of various chemical groups. The need for protection and removal of protection, and appropriate protective groups The choice can be easily determined by the skilled artist. The chemistry of the protecting group can be found in, for example, TW · Greene and P · αM · Wuts, the poor protection of the socks, 3rd edition, Wiley &amp; Sons, NewY. rk (1999), which is incorporated herein by reference in its entirety.The reaction can be monitored according to any suitable method known in the art. For example, the formation of products can be achieved by spectroscopic methods, such as nuclear magnetic resonance spectroscopy (such as 1H or 13c), infrared spectroscopy, spectrophotometry (such as UV-visible light) or mass spectrometry, or by chromatography, such as Monitoring by high performance liquid chromatography (HPLC) or thin layer chromatography. The compounds of the present invention can be prepared according to the methods described in this art for the preparation of amine diamines, their esters, and related compounds, such as those in U.S. Patent 4,537,773 and U.S. Patent 5,614,649. The entire text is incorporated herein by reference. In some embodiments, the compounds of the present invention can be made by successive coupling of three fragment components (F1, F2, and F3). 95014 -60- 200529810 F1 fragment The synthesis of the compound of the present invention may involve a boron-containing fragment (F1) having a structure represented by formula (A).

(A)

The dihydroxyborane ester moiety of F1 may include, for example, a glycol ester, such as those represented by an oxygen atom connected to a coil in formula (A). In formula (A), the stereochemistry of the carbon atom at the alpha position to the boron atom is controlled by the use of an asymmetric dimer radical to burn the ester group in the preparation of F1. For example, the pinanediol esters of 'dihydroxyborane can help the preparation of F1 fragments that are stereochemically pure or homosterically stereochemically pure. Taking the following as an example, the F1 fragment can be made in the following manner, in the presence of dichloromethane or dibromomethane, by making the compound of formula (B) (shown from the Ester) with a strong base (such as lithium diisopropylamine or lithium dicyclohexylamine) followed by the addition of a Lewis acid (such as Zη〇2, ZηΒι * 2 or FeCl3) to produce a compound of formula (C) (wherein l It is a halo group), which has a newly introduced three-dimensional center at the carbon at the position of para boron.

95014 -61-200529810

(C) A compound of formula (c) may be sequentially reacted with an alkali metal amine (such as lithium bis (trimethylsilyl) amine, sodium bis (trimethylsilyl) amine, and potassium bis (trimethylsilyl) amine ) Or other nucleophile reactions, which will effectively transform the newly formed stereocenter (for example, by the SN2 type mechanism), and introduce an amine group (NR2) to replace the halogen group (such as a gas group) to form the formula (D ) Compounds (wherein R may be, for example, alkyl, Si (alkyl) 3, aryl, or aryl).

(D) The compound of formula (D) can be further reacted with an agent capable of converting a group to Nh2 or a salt thereof to form an F1 fragment, which is substantially capable of coupling with another fragment via the amine. A suitable agent for the conversion of a hydroxyl group into NH2 may be a protic acid such as HC1, such as when R is a silyl group (e.g., trimethylsilyl). The compound of formula (B) can also be made according to a two-step procedure, which involves trialkoxy zeolite 'preferably triisopropoxyborane, which reacts with (1S, 2S, 3R, 5SH +) pinanediol' The mono-alkoxy [(18,23,3) 53)-(+) pinanediol] borane intermediate 'is obtained, in which the two alkoxy groups on the side of the bisoxy group have been replaced by (IS, 2 | §, 3r, pinanediol. This mixed pinanediol alkoxyborane, when reacted with an appropriate 95014 -62- 200529810 organometallic derivative such as Gri ^ RlcH2MgBr or alkylbenzene, The compound VII is obtained in good yield and purity. Starting from triisopropoxy hydrazone, the intermediate mixture is obtained as a mixture of isocyanate diol isopropyl f (F) and the compound of formula ⑻ f hoa /

Take the example A · 2 in this article as an example. R1 I h2c. Therefore, the present invention is further directed to a method for preparing a compound of formula (π): y ^ ° \ i R15a

R15c) R15d (II) 〇 The variable component is defined above, which is by the following method, a) the diol of formula (Π-b): H0 \ (R15a

P, R15b

D

R15c)

HO q (π-b) is reacted with a trialkoxyborane of the appropriate formula (Π-a): r17o ... C3_Cig cycloalkyl; under the conditions and conditions suitable for the formation of a mixed dioxo burnout intermediate of formula (II-c):

And make the intermediate of formula (II-c) under the conditions and conditions suitable for the formation of the compound of formula (11) 'and the reagent of formula R1 (¾ MXh a 1 regardless of i), where μ is a metal and halogen is Atom, or ii) a reagent of the formula R1 CH2Li. In some embodiments, R17 is q-C4 alkyl. In some embodiments, R17 is isopropyl. In some specific embodiments, the diol of formula (III-b) is pinanediol, pinacol, dicyclohexyl-1, Γ-diol, 1,2-ethanediol, 1,3-propanediol, 1,2-propanediol, 2,3-butanediol, ι, ι, 2,2 · tetramethylethanediol, ι, 2-diisopropylethanediol, 5,6-decanedidiol Alcohol, i, 2-dicyclohexylethanediol, dicyclohexyl-fluorene, i, -diol, diethanolamine, or 1,2-diphenyl-1,2-ethanediol. In some embodiments, the diol of formula (II-b) is a pinanediol. In some embodiments, the formula WCE ^ MX1 ^ 1 is a Grignard reagent. In some embodiments, the formula R1 CH2MXhal is R1 CH2MgBr. In some embodiments, R1 is isopropyl. In some embodiments, the present invention provides a method for preparing a compound of formula (Π-i): 95014 -64- 200529810

It includes: a) reacting (1S, 2S, 3R, 5S: K +) i-alkanediol with triisopropoxyborane under the time and conditions suitable for the formation of intermediates of formula:

And b) reacting the intermediate of formula (n-ii) with isobutyl magnesium bromide under conditions and conditions suitable for forming a compound of formula (11_ 丨). In some embodiments, the present invention provides a compound of formula (IHi)

The reaction step may be performed in any suitable solvent that is non-reactive to the reagents and the product and allows the reagents to be combined at a reduced temperature (e.g., a temperature cooler than room temperature). Suitable solvents include ethers such as dimethoxymethane, tetrahydrofuran, 1,3 · dioxolan, ι, 4-dioxolan, furan, ether, ethylene glycol dimethyl ether, ethylene glycol di Ethyl ether, diethylene glycol diethyl ether, diethylene glycol monoethyl ether, triethylene glycol dimethyl ether, toluene ether or tertiary-butyl ethyl ether. In some embodiments, the ether solvent contains tetrahydrofuran and / or ether. The reaction of the method described herein can be carried out at an appropriate temperature, which can be easily determined by a skilled technician. The reaction temperature is based on, for example, the temperature and boiling point of the reagent and the solvent 95014 -65- 200529810 if present; the thermodynamics of the reaction (eg, intense exothermic reactions may need to be performed at low temperatures); and the kinetics of the reaction (eg, high activation energy) The barrier may require high temperatures). "High temperature" means temperature above room temperature (approximately r ° c), and "low temperature" means temperature below room temperature.

In some embodiments, the appropriate temperature is a low temperature. The reaction of a trioxane with a diol to prepare a mixed trialkoxyborane intermediate can be carried out at a temperature of about -20 to about 10 ° C. In some embodiments, the reaction of trialkoxyborane and diol can be carried out at about TC. The reaction of the mixed trialkoxyborane intermediate with the organometallic reagent RiCH2MXhal or the alkyl lithium reagent r1cH2U can be Performed at, for example, a temperature of about -100 to about _2 (rc. In some embodiments, mixing a trialkoxyborane intermediate with 11110121 ^ 乂 1 ^ 1: the reaction is at about -78 C The reaction of the method described herein can be carried out in air or under an inert atmosphere. Typically, the reaction contains reagents or products that are substantially reactive with air, and air-sensitivity known to skilled technicians can be used. The synthesis technique is performed. B. F2 fragment The central segment of the compound of the present invention can be represented by fragment F2, which is coupled to the F1 fragment by peptide bond formation to form an F2-F1 intermediate. The compound is coupled via peptide bond or amidine bond The method is known in the art, and is described in, for example, Shuang · Fen #, Synthesis, Zuo #, Vol. 2, edited by Gross et al., University Press, 1979. An F2 fragment Examples are provided in formula (E) (pg is amine protected (R2 is defined herein). In addition, the protection of amino groups of amino acids using Boc or other amine protecting groups is known in the art from 95014 -66- 200529810.

〇 Η Pg / N

OH A compound of formula (E), which is an amino acid or an amino acid derivative, is commercially available or can be prepared by a routine method. For example, azaserine can generally be made by Hoffman rearrangement (Hoffinan's reaction) using, for example, aspartin, in which the amidine system of the aspartin side chain is converted to an amine (which can be subsequently protected) . Methods for Hoffman rearrangement of φ, such as for amino acids, are known in the art and are also provided in the examples below. In addition, azaserine can be made as disclosed in Zhang et al., Org. 1997, (52, 6918-6920. Boc-cyanoarginine derivatives can be made according to Wagenar et al., / Og · CAem. , 1993, Brother, 4331-4338. Synthesis of F2 fragment, where R2 is -CH2 CH2 CH2 NHC (= NR4) NH-Y, -CH2CONR5R6 &gt; -CH2NHCONR5R6 ^ -CH2NR9R10 ^ -CH (R7) ZR8 #, further disclosed in this article. F2 fragments can be obtained from commercial sources or made by methods known to those skilled in the art. Lu C. F3 fragments Another fragment (F3) can be obtained in any of various ways, such as by parenting Nuclear substitution or addition reaction, coupling to the F2 fragment of the F2-F1 intermediate, for example, F2 contains a nucleophilic group (such as an amine), and F3 contains an electrophilic group (such as CO, S02, etc.) and optionally Contains a leaving group (eg, aryl, hydroxy, alkoxy, alkylsulfonyl, arylsulfonyl, etc.). Examples of F3 fragments may have the formula RxCOXL, RxS02XL, RxNCO, or RxHCO (eg, Rx may be as described herein RA, RB, or Rc as defined in the above, and XL may be a free radical.) Coupling of RxCOXL (for example, when 95014 -67- 200529810 1 ^ is 011) to F2 -F1 intermediates can be performed according to standard procedures for peptide bond formation to prepare compounds having the formula F3-F2-F1, in which the F3 and F2 fragments are coupled via the amidine bond. In other specific embodiments, P3 and F2 can be coupled by a sulfonylamino chain, which is made by reacting rxs〇2Xl with an F2-F1 intermediate, where the amine moiety group on the F2_F1 intermediate replaces Rx S 〇2XL is for the radical. In addition, the reaction of the amine with the amine group of the F2_F1 intermediate can cause a urea chain (4ΙΝ (: ΌΝΗ〇, and Φ rXhc〇 and the amine of the F2-F1 intermediate The reaction of the base group, followed by the reduction of the formed imine group, can form an amine chain. Other coupling methods are known in the art and are also suitable. The F3 fragment can be obtained from Commercial sources or methods known in the art. Certain compounds of the present invention, in which R2 is 乂 CH2) dCH (R7) NR9R10, can be prepared in the following manner, removing the R10 amine bond, To form its corresponding deprotected compound, where R, H. This deprotected compound can be combined with a compound of formula R10a Reagent reaction of XL, in which R10a has the same meaning as R10 except Η, and it is a leaving group, such as a halogen group or a continuous acid derivative, φ or, where R and X _ ^ are used, meaning for example Reactive alkyl, carbocyclyl, or heterocarbocyclyl isocyanate, or alkyl, carbocyclyl, heterocarbocythrin, cyanocyanine, etc. For example, the compound of Example D 26 can be obtained from Example d It was prepared by removing and protecting the benzyloxyM group of 6, and Example VII was obtained, from which the serine nitrogen can be subsequently acylated. The present invention further provides a method for preparing a compound of 4 g ^ / 1 from seric acid (for example, wherein R 2 is NH 2). In general, air serine is produced by the removal of the major oxygen group (c (〇) QCH2 (C6H5)), which is connected to azaserine by 95014 -68- 200529810. A nitrogen of a group (for example, a compound of formula i, wherein R2 is -CH2NR9R10 'and envy is 11 and Ri0 is -c (= 〇) 〇CH ^ C6H5 ". Removal of benzyloxycarbonyl can be performed by, for example, hydrogenation The reagent is treated by reducing agent treatment. In some specific embodiments, the hydrogenation reagent contains H2, which is used in the presence of a metal catalyst (such as Pd / C 10%) depending on the conditions of October. The hydrogenation can be added to Shellfish fee, such as HC1, is performed in a suitable hydrogenation solvent containing, for example, an alcohol and / or an ether solvent. In some embodiments, the hydrogenation solvent contains an ether, such as 1,4-dioxolane. In a further specific embodiment, the hydrogenation solvent contains an alcohol, such as methanol. In a further specific embodiment, the hydrogenation solvent contains a mixture of an alcohol and an ether. An example of the preparation of the azaserine compound according to this method is, for example, Example D Provided in l7. Reaction parameters, including temperature, Force, atmospheric, based readily determined by one versed in the art of chemical synthesis of this person, and the progress of the reaction can be monitored by routine methods' include, for example, NMR. Accordingly, the invention provides a process for preparing a compound of formula (I) ··

(I) wherein: R1 is CrC6 alkyl, c2_c6 alkenyl, c2-c6 alkynyl, or 0: 7 cycloalkyl; R2 is -ch2nh2; soil Q is -b (orm) 2 or cyclic dioxo In vinegar, the cyclic C via stilbene ester contains 2 to 20 carbon atoms, and optionally contains a heteroatom that can be N, s 95014 200529810 or 0; alkyl, cycloalkyl, cycloalkyl Group, aryl or aralkyl group; χ is RA C (= 〇) _; RA is CVQo alkyl group optionally substituted by r2o; C2-C2G alkenyl group substituted by R2G as appropriate; optionally substituted by R2G c2-c2G alkynyl; optionally a carbocyclic group substituted with 1-5 R21; or% optionally a heterocarbocyclic group substituted with 1-5 R2 1; R2Q is selected from the group consisting of: -CN, halo, Haloalkyl-, Ci-q alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (= 〇) NH2, -S (= 0) 2NH2, -OH, -SH, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0) R2Ga, _NHC (= O) OR20a, -OR20a, -SR20a, -S (= O) R20a, -S (= 0) 2R2 () a, -S (= O) 2-NHR20a, -SC (= O) R20a ^ -C (= O) R20a ^ -C (= O) NHR20a ^ -C (= 〇) 〇-R20a &gt; _ -NHS (= O) 2R20a, -NHR20b, o-benzene Dimethyimidate,-(0-alkyl) r, -0-alkyl-OH, _ (0-alkyl) 011, -0112 (^, name 112 ()., -0-alkyl -R2Gc, -s_alkyl_r2 () c, _s (= o) _r2Gc, _SH)) 2-R20c, -S (= O) 2-NHR20c ^ -SC (= O) R20c '-C (= O) R20c &gt; -C (= O) OR20c &gt; -C (= 0) NHR2Ge, optionally a carbocyclic group substituted with 5 R21; and optionally a heterocarbocyclic ring substituted with 1-5 R2 1 Alkyl, C2-C20 alkenyl or C2-C20 alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally one or more radicals, q-C4 alkyl, aryl, heteroaryl Or -NHR2Gb substitution; 950U -70- 200529810 R2 () b is an amine protecting group; R2Ge is a carbocyclic group optionally substituted by 1-5 R22; or a heterocarbocyclic ring substituted by 1-5 R22 as appropriate R21 is selected from the group consisting of:

Ci_C20 alkyl, C2-C2Q fine, C2-C20 fast, C1-C20 alkyl, q-C20 thioalkoxy, -OH-CN, halo, haloalkyl, -NH2, _NH ( Alkyl), -N (alkyl) 2, -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 〇) 〇-φalkyl, -C (= 0) Alkyl, _S (= 0) _alkyl, -S (= 0) 2-alkyl, -S (= 0)-φ aryl, -S (= 0) 2-aryl, optionally 1- 5 R22 substituted carbocyclic groups and optionally 1-5 R22 substituted carbocyclic groups; R22 is selected from the group consisting of: q-Cw alkyl, C2-C10 alkenyl, C2-C10 alkynyl, phenyl , Halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, alkyl-oc (= o)-, alkyl-c (= o)- Aryl-0C (= 0)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH_, alkyl-C (= 0) NH-, alkyl-c (= 0) 0-, (alkyl-〇) r-alkyl, HO- (alkyl-0) r-alkyl-, _OH,% -SH, _CN, -N3, -CNO, _CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2NS (= 0)-, and H2NS (= 0) 2-; and r is 2, 3, 4, or 5; it includes: Under the conditions and conditions for which R2 is -CH2NH2, the compound of formula (I), the compound of formula (1), wherein 112 is -〇1 2 See 1-(: (= 0) € 〇12 ((: 6115), react with the appropriate hydrogenation reagent, provided that the hydrogenation agent is selective for the hydrazone of R2. 95014 -71-200529810 at In some specific embodiments, the hydrogenation agent is thallium, in the presence of HC1 in Pd / C 10% and M-dioxolane. Dihydroxyboronate / dibasic sideburning conversion contains dihydroxyborane ester Compounds of the present invention, such as pinanediol esters, can be hydrolyzed in any suitable manner to prepare the corresponding dihydroxyborane (-B (ΟΗ) 2) derivative. Hydrolysis conditions can include the use of dihydroxyborane esters Contact with an excess acid, such as a protonic acid, such as HC1. Conversely, dihydroxyborane can be esterified by contacting an acid compound (_β (〇η) 2) with an alcohol such as a diol for a sufficient time to produce its corresponding Ester. The esterification reaction can be acid or catalyzed. The invention will be described in more detail by specific examples. The following examples are presented for illustrative purposes and are not intended to limit the invention in any way. Those skilled in the art will It is easy to understand that a variety of non-critical parameters can be changed or modified to produce Basically the same result. [Embodiment] Examples Example A.1 (111) _1 _ [(3 略 48,68々11) _hexaargon_3 &amp; 5,5-trimethyl_4,6-methylalkyl -1,3,2_Benzodioxy butterfly Wuyuan_2_yl] -3_methylbutylamine hydrochloride Synthesis Step 1 · 2- (2-methylpropyl)-(3 (28 , 48 wind 7 (211) -hexahydro-3 € 1,5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxoline

A mixture of panthanediol (23.9 g, 0.140 mol) and 2-methylpropyldihydroxyboron 95014 -72- 200529810 (15 g '0.147 mol) in ethyl acetate (300 ml) , And stirred at room temperature for 24 hours. The mixture was dehydrated and dried over anhydrous sodium sulfate, and purified by column chromatography (silica gel 230-400 mesh), and the mixture was dissolved with hexane: ethyl acetate 90:10. The product was obtained as a clear oil (32.6 g, 94% yield). ^ NMRCDMSO- ^): 4.28 (1H5 dd5 J = 8.8 Hz5 2.0); 2.30 (lH5m); 2.18 (lH, m); 1.96 (lH, t, J = 5.3); 1.86 (lH, m); 1J8 (1H , Combination, J = 6.8); 1.68 (1H, m); 1.30 (3H, s); 1.25 (3H, s); 1.01 (1H, d); 0.9 (6H, d) , J = 6.6); 0.81 (3H, s); 0.69 (2H, m). Step 2: 2-[(lS) -l-chlorotolylmethylbutyl] -like 3,43 wind 7 (1 noisy Hexahydro-3 (1,5,5-trifluorenyl 4,6-methanyl-1,3,2-phenylhydrazine

By adding a 10.0M solution of butyllithium in hexane (25.4 ml, 0.254 moles) to diisopropylamine (35.7 ml, 0.254 moles) in anhydrous tetrahydro A solution of lithium diisopropylamine in a solution at -5 (rc) in bitumin (60 ml) was prepared, and the temperature was raised to -30 ° C. This solution was transferred via a cannula to step 1 of 2- ( 2-methylpropyl ^ chenglaifeng ~ Hexahydro also ^ trimethyl ^ branyl-1,3,2 · benzodioxine (50 grams, 0.212 moles) and CH2C12 (50 Ml, 0.848 mol) in a solution of anhydrous tetrahydrofuran (700 ml), while keeping the temperature below -70. (:. Then, add a 1.0 M solution of anhydrous zinc chloride in ether (339 ml, 〇_339mol), while maintaining the internal temperature below -70 ° C over a period of 30 minutes. The reaction mixture was stirred at _78t for 3 hours 95014 -73 · 200529810 and then 'warned' to warm to room temperature After removing the solvent by rotary evaporation, the residue was separated between petroleum ether (1000 ml) and 10% ammonium chloride aqueous solution (800 ml). Petroleum ether (300 mmol) ) The aqueous layer was further extracted. The combined organic phases were dehydrated, dried over anhydrous sodium sulfate, and concentrated. The product was obtained as a brown oil (59.0 g, 98% yield) containing about 9% mole / mole of starting material (1 H-NMR), and it was used in subsequent steps without further purification. Xin H NMR (DMSO-d6). 4.43 (1H, dd5 J = 8.85 1.8); 3.59 (1H, m); 2.33 (1H, m), 2.21 (lH, m); 2.01 (1¾ m); 1.88 (lH, m); 1.84-1.55 (5H, m); 1.34 (3H, s); 1.26 (3H, s); 1.09 (1H, J = 10.1); 〇9 (3H, d, j = 68); 〇87 (3H, d, J = 6.4); 0.82 (3H, s); Step 3: Gu-bis (trimethyl Silyl h (1R) small [(3aS, 4S, 6S, 7aR) hexahydro-3a55_ dimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] Methylbutylamine

Add a 10M solution of lithium bis (dimethylsilyl) amine in tetrahydrofuran (189 pens, 0.189 moles) to the crude 2 _ [(ls) small chloro_3_methylbutyl group in step 2 ]-(3 &amp; 3,43,68々11) -hexahydro_3 \ 5,5-trimethyl_4,6-methylalkyl-1,3,2-benzodioxoborofluoride (59.0 g , 91% purity, 0.189 mol) in a solution of tetrahydrofuran (580 耄 liters) for 30 minutes, while cooling at _7yc. Warm the reaction / cardiosome to room temperature overnight. The solvent was removed by rotary evaporation and the residue was dissolved in anhydrous hexane (800 ml). The resulting suspension 95014-74-200529810 was stirred at room temperature for 2 hours, and then the solid was removed on the diatomaceous earth cake by filtration. The diatomaceous earth cake was dried with anhydrous hexane (3 X 100 ml). )washing. The filtrate was concentrated and a satisfactory pure product was obtained in practical quantitative yield as a brown oil (79 g). The product was used in subsequent steps without further purification. iHNMRpMSO-dg): 4.33 (lH, dd, J = 1.5 Hz, 8.6); 2.58 (lH, m); 2.29 (1H, m); 2.18 (lH, m); 1.95 (lH, t, J = 5_9); 1.85 (lH, m); 1.9-1.55 (3H, m); 1.31 (3H, s); 1.24 (3H, s); 1.17 (lH, m); 1.01 (lH, d, J = 10.6); 0.85 (3H, d, J = 6.6), 0.83 (3H, d, J = 6.6); 0.80 (3H, s); 0 · 08 (18H, s). Step 4: (1 Magic-1- [(3 (13,43,68,7 € ^)-hexahydro-3 (1,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy butterfly -2-yl] -3-methylbutylamine hydrochloride

The crude n, N-bis (trimethylsilyl small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl_4,6_methylalkyl-1, 3,2-benzodioxofluoren-2-yl] each φ methylbutylamine (79 g '0.193 mol) in a solution of dioxolane (loo ml) and ethyl scale poo ml) A 4N solution of hydrogenated hydrogen in dioxin (193 ml, 0.7772 mol) was added, and at the same time, it was cooled down. Then, the mixture was stirred at room temperature for 4 hours, and concentrated. The residue was dissolved in anhydrous ether (500 ml), and a 2 m solution of hydrogenated hydrogen in ether (⑽mL, 0.096 mol) was added. The mixture was stirred at 0 ° C for 1 hour and then concentrated. The residue was dissolved in anhydrous hexane, and the resulting suspension was stirred at room temperature overnight. The solid was collected by filtration and dried under vacuum to obtain 38.1 95014 -75- 200529810 g of product (66% yield). The second recovered product (4.13 g, 7% yield) was obtained from the mother liquor. 1H NMR (DMSO-d6): 7.85 (3H, br); 4.45 (1H, dd, J = 9.2 Ηζ); 2.78 (1H, m); 2.34 (lH, m); 2.21 (lH, m); 2.01 (lH, t, J = 5.3); 1.89 (lH, m); 1.82-1.65 (2H, m); L49 (1H, m); 1.38 (3H, s); 1.27 (3H, s); U2 (1H, d, 1_12); 0_87 (6H, d, J = 6.6); 0.83 (3H, s) · Example A.2 2- (2 • methylpropyl) _ (3 &amp; 8,48,68 , 7 &amp; 11) -Hexargon-3 \ 5,5_trimethyl_4,6_methylalkyl_1,3,2_benzodioxoborohydride Alternative synthesis step 1: 2- (1- (Methylethoxy)-(36 ^, 48,68,76111) -hexahydro-3 (2,5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazine Oxygen

In a solution of (1S, 2S, 3R, 5S)-(+)-alkanediol (50.0 g, 0.293 mol) in anhydrous tetrahydrofuran (350 ml), slowly add triisopropoxy to the pot, On the same day, Ding's hand was awarded at 0 C and Qi. After 2 hours' the solvent was removed by rotary evaporation. The oily residue was redissolved in hexane (150 ml) and passed through a tear solution 'to remove a very small amount of white solid. The liquid was concentrated by rotary evaporation to obtain the product as a clear oil (62.6 g, 90% yield). 'HNMRCDMSO ^): 4.31-4.20 (2H, m); 2.34 ^ 2.16 (2H, m); 1.96 (1H, t, J = 5.5); 1.90-1.85 (lH, m); 1.74-1.67 (lH, m) ); 1.32 (3H, s); 1.31 (1Η, d, J = 7.6); 1.25 (3H, s)]. 14 (3H, d, J = 6.1); 1.13 (3H, d, J = 6.1); 〇 · 81 (3H, s). Step 2 ·· 2- (2-methylpropyl) -caffeine 3,48,68 &gt; 11) -hexahydro-3 € 1,5,5_tri Yin Ji 4,6 ^ alkynyl-1,3,2-phenylhydrazone dioxo code 95014 -76 · 200529810

Add the 2M solution of isobutyl desertification in the second test (131 · 5 ml, 0.263 mol) within 1 hour, and add it dropwise to the 2- (μmethylethyl) obtained in step 1. K3aS34S? 6S57aR) ^ A .3a55? 5- f ^ ^ 6-f ^ ^ 4

Oxygen (62.6 g, 0.263 moles) in a solution of anhydrous tetrahydrosquench (33 ml), ㈣, ㈣ 耽 under nitrogen. The mixture was then allowed to warm to room temperature and then transferred to a mixture of 2 N sulfuric acid (150 ml) and diisopropyl ether (250 ml). After stirring for 10 minutes, a saturated solution (100 ml) was added, and the layers were separated. The organic phase was washed with brine (100 mL), dried over sodium sulfate, and concentrated. The residue was purified by column chromatography (silica gel) and dissolved in 5% ether in hexane. The product was obtained as a clear oil (38.45 g, 62% yield). Example B.1 Amine methyl 1,1-dimethyl ethyl ester, N-[(iSH-[[[(iRH _ [(3aS, 4S, 6S, 7aR) 4 Argon-3a, 5,5-Trimethyl -4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Benzyl 4 _ [[Imine (Songyl Amine) methyl] amino] butyl

Method A. · HOAt / HATU 95014 -77- 200529810 in a solution of BocNH (N02) ArgOH (15.7 g, 49.3 mmol) in anhydrous DMF (100 ml), add HATU (hexafluorophosphate 〇_ (7- Nitrobenzotriazole small group) -1,1,3,3-tetramethylpyrene; 18.7g, 49.3 millimoles) and HOAt (1-hydroxy-7-nitrobenzotriazole; 6.71 G, 49.3 millimoles). The mixture was cooled to 0 ° C. and N-methylmorphine (13.6 ml, 0.123 mol) was added. After 10 minutes, (lR) -l-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1 of Example A.1 was added , 3,2-benzyldioxocarbox-2-yl] -3-methylbutylamine hydrochloride (12.4 g, 4U mol). The cooling bath was removed and the mixture was stirred at room temperature for 4.5 hours. The mixture was diluted with ethyl acetate (800 ml) and washed with 2% citric acid solution (2 X 150 ml), 2% NaHC03 solution (2 X 150 ml), and 2% NaCl solution (2 X 150 liters). The aqueous phase was further extracted with ethyl acetate (150 ml). The combined organic phases were dried over sodium sulfate and concentrated. The formed oily residue was redissolved in ethyl acetate (500 ml), and the solution was washed with cold water (200 t liter). The aqueous phase was further extracted with ethyl acetate (500 ml). The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in diethyl ether (100 ml) and the solution was slowly added to hexane (600 ml) while stirring. A white solid (43.4 g) was collected by filtration and purified by column chromatography. First, a 50:50 hexane: ethyl acetate mixture was used, and then it was dissolved with ethyl acetate. The product-containing fractions were concentrated, the residue was dissolved in ether (100 ml), and the resulting solution was slowly added to hexane (600 ml)

While stirring. A white solid was collected by filtration (15.2 g, 66% yield). Method B: To a suspension of IBCF in BocNH (N0) ArgOH (5.82 g, 18.2 mmol) in anhydrous dioxane (100 ml), add N-fluorenylmorpholine (2 0 Ml, 18.2 95014 -78- 200529810

Mol). The mixture was allowed to cool to -15 ° C, and then isobutyl formate (2.37 ml '18.2 mmol) was added. Mix the mixture at _15. Stir at 10 ° C for 10 minutes, and then 'Add (1R) small [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6 as obtained in Example A · 1 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutylamine hydrochloride (5.0 g, 16.6 mmol), then immediately add another N- Methylmorpholine (2.0 ml, 18.2 mmol). The reaction mixture was stirred at -15 ° C for 1.5 hours, then allowed to warm to room temperature and worked between ethyl acetate (150 ml), water (150 ml) and 0.1 N hydrochloric acid (10 ml). Separation. The organic phase was washed with a saturated NaHC03 solution, dried over anhydrous sodium sulfate, and concentrated. The oily residue (9.25 g) was purified from ethyl acetate by crystallization to obtain three recovered products as a satisfactorily pure product (5.03 g, 54% yield). iHNMRpMSO-dg): 8.80 (lH, br); 8.50 (lH, br), 7.87 (2H, br); 7.01 (lH, d, J = 7.9), 4.07 (lH, dd, J = 7.9); 4.0 ( lH, m); 3.12 (2H, m); 2.55 (1Η, m); 2.2 (lH, m); 2.01 (lH, m); 1.83 (lH, t, J = 5.1); 1.78 (lH, m); 1.74-1.44 (7H, m); 1.38 (9H, s); 1.33 (lH, d, J = 10.3); 1.24 (5H, s); 1.22 (3H, s); 0.84 (6H? d? J = 6.6); 0.81 (3H, s). Example B.2 Aminomethyl acid 1,1-dimethylethyl ester, N-[(lS, 2R) -l-[[[(lR) -l- [(3aS, 4S, 6S, 7aR) _ hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzobenzodioxo-2-yl]- 3-methylbutyl] amino] carbonyl] -2_hydroxypropyl]-95014 -79- 200529810

Boc-L-threonine (870 mg, 3.97 mmol, 1.2 eq.) Was dissolved in anhydrous DMF (30 liters) at room temperature. To this solution was added tbtu (tetrafluoroborate N, N, N ', N, -ramethyl · 0- (benzotriazole small group) fluorene; 1270 mg, 3.97 mmoles, 1.2 equivalents ) And allow the mixture to cool at 0-5 ° C. Then, Tim added NMM (0.9 ml, 8.27 mmol, 2.5 equivalents) and Example A.1 of (1R) -1_ [(338,48 wind 7 &amp; 10-hexahydro-3 &amp;, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenbutamine hydrochloride (1000 mg, 3.3 mmol , 1 equivalent). The mixture was stirred at room temperature for 16 hours, then extracted with ethyl acetate (100 ml), and washed with the following solution: citric acid 2% (50 ml), sodium bicarbonate 2% (50 Ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to obtain 1290 mg of a glassy solid. The yield was 84.3%.

25-30 ° C ^ NMRCDMSO-dg): 8.88 (lH, br); 6.49 (1H, d5 J = 8.4 Hz); 4.88 (1H5 d5 J = 5.8); 4.05 (lH, dd); 3.93 (lH, m); (lH, m); 2.51 (lH, m); 2.19 (lH, m); 2.01 (lH, m); 1.83 (lH, t, J = 5.9), 1.78 (lH, m); 1.68 ( lH, m); 1.62 (1H, m); 1.39 (9H, s); 1.34 (lH, d, J = 10.0); 1.24 (3H, s); 1.22 (3H, s); 1.06 (3H, d, J = 6.4); 0.85 (6H, d, J = 6.4); 0.80 (3H, s) · Example B.3 Other intermediate compounds 95014 -80- 200529810 The intermediates reported below start with the appropriate intermediates and follow One of the procedures described in Examples B · 1 and B_2 was made. (2S) -2-[(l, l-dimethylethoxycarbonyl) amino] stearylpentanamine, N _ [(1R) small

[(3 (^, 43 wind 7〇! 1) -hexahydro-3 (1,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride- 2-yl] -3-methylbutyl]

Confrontation

iHNMRpMSOO: 8.85 (lH, br); 7.01 (lH, d, J = 8.0 Hz); 5.9 (lH, t, J = 5.7); 5.36 (2H, bio; 4.03 (2H, m); 2.93 (2H, m); 2.19 (lH, m); 2.0 (1H, m); 1.83 (lH, t, J = 5.3); 1.78 (lH, m); 1.68 (lH, m); 1.62 (lH, m); 1.52 (2H, m); 1.38 (9H, s); 1.33 (1H, d, J = 9.9); 1.24 (3H, s); 1.22 (2H, s); 0 · 86 (3H, d, J = 6.6) ; 0.84 (3H, d, J = 6.6); 0.80 (3H, s) · (2S) each (aminocarbonyl) -2-[(l, l-dimethylethoxycarbonyl) amino] propyl Amidine, N- · [(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifyl-4,6-f alkyl-1,3,2 -Benzobenzodioxo-2-yl] dongmethylbutyl]

1H NMR (DMS0-d6): 8.74 (lH, br); 7.28 (lH, br); 6.95 (2H, m); 4.36 (1H, 95014 -81-200529810 m); 4.07 (1H, m); 2.55 ( 1H, m); 2.38 (2H, m); 2.2 (1H, m); 2.02 (2H, m); 1.84 (lH, t, J = 5_5); (lH, m); 1.79 (lH, m ); 1.68 (lH, m); 1.63 (lH, m); 1.38 (9H, s); 1.33 (lH, d, J = 10); 1.24 (3H, s); 1.22 (2H, s); 0.85 ( 3H, d, J = 6.4); 0.83 (3H, d, J = 6.4); 0.81 (3H, s). Aminomethyl methanoate, N-[(1S, 2R) small [[[( 1R) small [(3 (^, 43,68,7 € 1 p-hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] each methylbutyl] amino] carbonyl] -2-hydroxypropyl]

57-60 ° C · 1H NMR (DMSO-d6): 8.66 (1H, s); 7.40-7.29 (5H, m); 7.09 (1H, d, J = 8.75); 5.06 (2H, s); 4.90 (1H, J = 5.68); 4.11-3.99 (2H, m); 3.91-3.77 (1H5 m); 2.58-2.53 (1H, m); 2.26-2.14 (1H? m); 2.07-1.97 (1H, s); 1.84 (lH, t, J = 5.52); 1.81-1.75 (lH, m); 1.73-1.58 (2H, m); 1.33 (2H, d, J = 10.1); 1.27-1.20 ( 7H, m); 1.06 (3H, t, J = 6.27); 0.91-0.79 (9H, m). Example B · 4 (2S) -2-[(l, l-dimethylethoxycarbonyl) amino ] Each (4-methylphenylfluorenyl) amino 1 propanamide, N-[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2 · benzodioxofluoren-2-yl] -3-methylbutylbenzene

95014 -82-200529810

(2S) -2-[(l, l-dimethylethoxycarbonyl) amino] of each of G.6 [(4-methylbenzyl) amino] -propionic acid (650 mg, 2 mmol, ι · 2 equivalent), dissolved in anhydrous DMF (15 ml) under nitrogen, and TBTU (640 mg '2 mmol, ΐ · 2 equivalent) was added at room temperature. Allow the mixture to cool down in an ice bath and add NMM (0.55 ml, 5 mmol, 2.5 eq.) And the (claw) of Example A.1 [(Sec. ;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutylamine hydrochloride (500 mg , 1.65 millimoles, 1 equivalent). The mixture was stirred overnight, poured into water (200 mL), and extracted with ethyl acetate (100 mL). The organic layer was washed with the following solutions: 2% citric acid (20 ml), 2% sodium bicarbonate (20 ml), 2% NaCl (20 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated to give 740 mg of a glassy solid (quantitative yield). 1HNMR (DMSO-d6) 8.76 (lH, br); 8.28 (1H, t, J = 5.31 Hz); 7.71 (2H5d, J = 7.9); 7_26 (2H, d, J = 7.9); 6.97 (lH, d , J = 8.0); 4.27 (lH, m); 4.07 (lH, dd, J = 8.2,1.5); 3.48 (2H, m), 2.58 (lH, m); 2.35 (3H, s); 2.19 (lH , M); 2.02 (lH, m); 1.83 (lH, t, J = 4.9); l / 78 (lH, m); 1.62 (2H, m); 1.35 (12H, m); 1.24 (3H , S); 1 · 23 (3H, s); 0.82 (3H, d); 0.80 (3H, d); 0.78 (3H, s) · Example B.5 2-S-[(l, l-dimethylformate (Ethoxyethinoyl) amino] each (hexylamino) -propanilamine, N- 丨 (1S) _1 [[(111) 小 [(3 Note 8,48,68,7 said) -hexahydro -Known, 5,5_trimethyl_4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] 95014 -83- 200529810

Each of Example G.7-2 [(1,1-dimethylethoxycarbonyl) amino] -3- (hexamidineamino) propionic acid (300 mg, 1 mmol, 1.2 equivalents) was placed under nitrogen Dissolve in anhydrous DMF (25 ml) and add TBTU (318 mg, 1 mmole '1.2 equivalents) at room temperature. The mixture was cooled in an ice bath at 0-5 ° C, and NMM (0.27 ml, 2.47 mmol, 2.47 equivalents) and (1R) -l-[(3aS, 4S, 6S, 7aR) ) -Hexahydro-3a, 5,5_trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutylamine hydrochloride (250 mg, 0.82 mmol, 1 equivalent). The mixture was stirred for 3 hours, poured into water (150 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with the following solutions: citric acid 2% (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated to give 450 mg of a glassy solid. Yield was quantified. Analytical data: ^ NMR (DMSO-d6). ΔΗ: 8.71 (lH, brd, J = 2.6 Hz); 7.73 (lH, brt, J = 5.9 Hz); 6.81 (lH, d, J = 8.2); 4_10 ( 2H, m); 3.24 (2H, m); 2.56 (lH, m); 2.19 (lH, m); 2.03 (3H, m); 1.83 (lH, t, J = 5.5); 1.78 (lH, m) ; 1.64 (2H, m); 1.47 (2H, m); 1.36 (9H, s); 1.4-1.15 (9H, m); 1.24 (3¾ s); 1.21 (3H); 0.83 (9H, m); 0.79 (3H, s). Example B.6 95014 -84- 200529810 2_S _ [(1,1-Dimethylethoxycarbonyl) amino group 3- (4-Lanthylsulfonylamino) propylamine, bucket [(18) small [[(111) small [(3 &amp; 8,48,68,7 &amp; 11) -hexahydro_33,5,5_trimethyl_4,6_methanyl_1,3 , 2_benzodioxoborohydrin_2_yl] _3_methylbutyl] amino] several groups]

Example G.8, 2-S-[(l, l-Difluorenylethoxyquinyl) amino] · 3- (4-macrofluorethenylamino) propionic acid (1.39 g, 3.83 mmol, 1.2 (Equivalent) was dissolved in anhydrous DMF (20 ml) under nitrogen, and TBTU (1.23 g, 3.83 mmol, 1.2 equivalent) was added at room temperature. The mixture was cooled in an ice bath at 0-5 ° C, and NMM (1 ml, 9.57 mmol, 3 equivalents) and Example A · 1 (lRH _ [(3aS, 4S, 6S, 7aR) -hexahydro) were added. -3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl> 3-fluorenylbutylamine hydrochloride (0-96 g, 3.19 millimoles, 1 equivalent). The mixture was stirred for 2 hours, poured into water (200 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with the following solution ... 2% citric acid (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated with ether to give 1.5 g of a white solid. Yield 77 Analytical data: ^ NMR (DMSO-d6). ΔΗ: 8.54 (1H, d, J = 2.9 Hz); 7.91 (2H, m); 7.75 (1H, t, J = 5.9); 7.50 (2H, t, J = 8.8); 6.83 (1H, d, J = 8.4); 4.19 (1H, bf d, J = 8.2); 95014 -85- 200529810 4.14 (m, m); 3.01 (2H , M); 2.69 (lH, m); 2.25 (lH, m); 2.09 (lH, m); 1.90 (lH, t, J = 5.7); 1.85 (lH, m); 1.8-1.6 (2H, m ); 1.5-1.2 (5H, m); 1.43 (9H, s); 1 · 29 (6H, s); 0.89 (6H, d, J = 6.4); 0.86 (3H, s) · Example B.7

2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (3,4-dimethoxyphenylacetamido) propanamidin, N-[(1S) _1 -[[(1R) 小 [(3aS, 4S, 6S, 7aR) · Hydrogen-3a, 5,5-trimethyl • 4,6-Methylalkyl-1,3,2-benzodioxo Fluoren-2-yl] -3-methylbutyl Iamino] carbonyl] hydrazone 5

Y rNVS

° VNH Ο Ο

I Make Example G.9 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (3,4-dimethoxyphenylacetamido) -propionic acid ( 0.73 g, 1.90 mmol, 1.2 eq), dissolved in anhydrous DMF (20 ml) under nitrogen, and TBTU (0.61 g, 1.90 mmol, 1.2 eq) was added at room temperature. The mixture was cooled in an ice bath at 0-5 ° C, and NMM (0.52 ml, 4.7 mmol, 2.5 equivalents) was added to (1R) of Example A.1 [(3 &amp; 3,48,68,7 & amp 11) -Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutylamine hydrochloride (〇 47 grams, 1.6 millimoles, 1 equivalent). The mixture was stirred for 2 hours, poured into water (200 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with the following solutions: 2% citric acid (50 ml), 2% sodium bicarbonate (50 ml), 2% NaCl (50 ml). 95014 -86- 200529810 The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated with diethyl ether to obtain 0.95 g of crude product, which was purified by silica gel chromatography (eluent ethyl acetate) to obtain 0.3 g White foam. The yield is 30%. Analytical data: TLC silicone (100% ethyl acetate, R.f &gt; 0.50) ^ NMR (DMSO-d6).

: 8.69 (1H, d, J = 2.6 Hz); 7.90 (1H, t, J = 5.7); 6.85 (2H, m); 6.74 (1H, dd, J = 1.5, 8.1); 6.85 ( 3H, m); 4.12 (2H5m); 3.73 (3H, s); 3.72 (3H? S); 3.34 (2H, s); 3.31 (2H, m); 2.58 (1H, m); 2.20 (1H, m); 2.03 (1H, m); 1.85 (1H, t, J = 5.3); 1.79 (1H, m); 1.66 (2H, m); 1.38 (9H, s); 1.40_1 · 15 (3H, m); 1.25 (3H, s); 1.23 (3H, s); 0.83 (6H, d, J = 6.6); 0.81 (3H, s) · Example B.8 2-S- [(l, l-dimethylethoxycarbonyl) amino] -3- (3-phenylureido) propanamide,] \-[(18) -l-[[(lR) -l _ [(3aS , 4S, 6S, 7aR) -hexaargon_3a, 5,5-trimethyl_4,6_methylalkyl_1,3,2 · benzodioxofluoren-2-yl] _3_methylbutane [Amino] carbonyl]

Let Example 2 of Example G.10 each [(1,1-difluorenylethoxycarbonyl) amino] -3- (3-benzylidene) propanoic acid (0.41 g, 1.26 mmol, 1.2 equivalents) be Under nitrogen, dissolved in anhydrous DMF (20 ml), and TBTU (0.40 g, 1.26 mmol, 1.2 equivalents) was added at room temperature. The mixture was cooled in an ice bath at 0-5 ° C, and NMM (0.346 ml, 3.1.5 mmol, 2.5 eq.) And (1R) -l-[(3aS, 4S, 6S) of Example A.1 were added , 7aR)-

95014 -87- 200529810 Hexahydro-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] 3 methylbutylamine salt Acid salt (0.31 g '1 millimolar ,! equivalent). The mixture was drained for 2 hours, poured into water (200 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with the following solutions: 2% citric acid (50 ml), 2% sodium carbonate (50 ml), and 12% NaC (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated with diethyl ether (50 ml) to obtain 0.58 g of a white solid. The yield was 96.6%. φ Analytical data: TLC silicone (100% ethyl acetate, r f = 0.47), dazzling point 128-130. . ^ NMR (DMSO-d6). (5H: 8.79 (1H, d, J = 2.7 Hz); 8.69 (1H, s); 7.38 (2H, d, J = 7.9); 7.22 ( 2H, t, J = 8.1); 7.00 (lH, d, J = 8.1); 6.90 (lH, t, J = 7.3); 6.16 (lH, t, J = 5.7); 4.12 (2H, m); 3.45 (lH, m); 3.17 (lH, m); 2.60 (lH, m); 2.21 (lH, m); 2.04 (lH, m), 1.85 (lH, t, J-5.3), 1.79 (lH, m ); 1.66 (2H, m); 1.38 (9H, s); 1.40-1 · 15 (3H, m); 1.26 (3H, s); 1.23 (3H, s); 0.84 (6H, d, J = 6.6 ); 0.81 • (3¾ s). Example B.9 Synthesis of other compounds According to the procedure of Example B.4-B.8, the following compounds can be obtained by making (lR) -l-[(3aS, 4S) , 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl_4,6_fluorenylalkyl3,3,2 · benzodioxofluoren-2-yl] -3-methylbutylamine Hydrochloride was prepared by reacting with the intermediates of Examples G11, Gj2, and G.13. 95014 -88- 200529810 B.9.1 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3 -(Acetamido-) propanamidin, hydrazone [(18) small [[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl- 4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] several groups]. B.9. 2 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3-(9-fluorenylmethyloxyaminemethylamidino) ethyl] -propanamide, N-[( lS) -H [(lR) -l-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone Dioxolium-2-yl] -3 "methylbutyl] amino group] · 0 ^) B.9.3 2-S-[(l, l-dimethylethoxycarbonyl) amino group]- 2-[(pentylureido) ethyl] -N-[(lS) -l-[[[((lR) -l-[(3 &amp; 8,43,63,7 &amp; 1〇-hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl]-/ -N ° B.9.4 2-S-[(l, l-dimethylethoxycarbonyl) amino] -2- (methanesulfonylamino) ethyl] -N-[(1S) small [[[ (111) -1-[(333,43,63,7311) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxide 2-yl] -3_fluorenylbutyl] amino] woven group]-o = s = o 1 B.9.5 2 each [(1,1-dimethylethoxycarbonyl) amino] -2- [ (Ethoxycarbonylsuccinoyl) -amidino] ethyl] -N-[(lS) -H [[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] weiyl ]-B.9.6 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (methyloxyaminomethyl) ethyl] -propanilamine, 1 ^ [(13 ) -1-[[(11〇 小 [(3 &amp; 8,43,68,7 &amp; 11) -hexahydro-3a, 5,5-dimethyl-4,6-fluorenyl-1,3, 2-Benzamidinedioxolane-2-yl] -3-methylbutyl] monthlyyl]. 6 95014 -89- 200529810 Example B · 10 Aminomethyl acid 1,1-dimethyl Ethyl ester, N-[(lS, 2R) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexaaza-3a, 5,5-trimethyl-4,6 -Methylalanyl-1,3,2-benzodioxo-fluorenyl-2_yl] _1_fluorenylbutyl] amino] carbonyl] -methyl

B.9.7 2 each [(1,1-dimethylethoxycarbonyl) amino] -3 丄-[2- (1Η-pyrazole) ethyl] -N-[(1S) -1-[[[ (1R) -1 \ | HS-[(3aS, aS, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Boron-2-yl-]-3-methylbutyl] amino] amino] This compound has been obtained from (1R) of Example A.1 [(3 &amp; 3,43,68,7 &amp; 11) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] each methylbutylamine hydrochloride and Commercially available N- (1,1-dimethylethoxycarbonyl) glycine was prepared according to the procedure of Method B of Example B.1. 1H-NMR (DMSO-d6): 8.84 (1H, s); 7.08 (1H, t3 J = 5.93 Hz); 4.06 (1H, d, J = 7.48 Hz); 3.67 (2H, t, J = 5.32 Hz) ; 2.60-2.48 (1H, m); 2.24-2.16 (1H, m); 2.06-1.96 (1H, m); 1.84 (1H, t, J = 5.50 Hz); 1.82-1.76 (1H, m); 1.74 -1.58 (2H, m); 1.39 (10H, bs); 1.23 (9H, d, J = 8.18 Hz); 0.87-0.83 (6H, m); 0.82 (3H, bs). Example Cl (2S) -2-amino-5-[[imino (nitroamino) methyl] amino] pentamidine, N _ [(1R) small [(3 Note 8, 48, 68, 7 &amp; 11) _Hexahydro-3,5,5_trimethyl_4,6-methylalkyl-1,3,2-benzodioxane 95014 -90-200529810 Boron-2-yl]- 3-methylbutyl]; hydrochloride

Method A: A 4N solution of hydrogen chloride in dioxolane (15 ml) was added to the amine methyl acid U-dimethylethyl ester of Example B.1, N-[(1S) -1-[[[( 1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2- [] Methyl] -3-methylbutyl] amino] carbonyl] ice [[imine (seminino) methyl] amino] butyl]-(4.04 g, 7.06 mmol) in dioxo The solution in a mixture of osmium (40 ml) and diethyl ether (7 ml) was simultaneously cooled at 0 ° C. The reaction mixture was allowed to warm to room temperature 'and stirred for another 4 hours. The solvent was removed by rotary evaporation, the residue was treated with diethyl ether (50 ml), and the mixture was stirred at room temperature for three days. The formed solid was collected by filtration to obtain 318 g of pure product (90% yield).

Method B: The amine methyl acid 1,1 -dimethyl ethyl ester of Example B · 1, and the ketone exosome is called small _3,48,68,7311) -hexahydro-3tun 5,5-trimethyl -4,6-methylalanyl-1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] · amino] provinyl] -4-[[imino (Aminoamino) -methyl; l.amino] butyl]-(3 g, 5.3 mmol), dissolved in 0 (40 ml), and at 0 ° C under nitrogen A solution of about 10% HC1 in 0 (20 ml) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for another 5 hours. The solvent was decanted to 95014 -91-200529810, and the residue was washed twice with Et20 (20 ml) and dried in vacuo to give the title compound as a white powder (2.43 g, yield 91%). 1H NMR (DMSO-d6): 8.56 (2H, br); 8.22 (3H, br); 7.97 (2H, br); 4.28 (lH, dd, J = 8.6Hz, 2.01); 3.77 (lH, m); 3.04 (lH, m); 2.28 (lH, m); 2.11 (2H, m), 1.92 (1H, t, J = 5.5); 1.83 (1H, m); 1.79-1.59 (4H, m); 1.59-1.37 (3H, m); 1.31 (4H, s); 1.24 (3H, s); 1.19 (1H, d, J = 10.4); 0 · 88 (3H, d, J = 6.0); 0.86 (3H, d, J = 6.0); 0.81 (3H, s).

Example C.2 Dihydroxyborane, [(1R) -1 _ [[(2S) _2 · amino-5 · [[imino (nitroamino) methyl I aminofluorenyl-ketopentyl] Amine] _3_methylbutyl], hydrochloride

Let the amine methyl acid 1,1-dimethyl 6_, N-[(1S) -H [[(1R) -1-[(3 &amp; 3,43,7 &amp; 11) -six) of Example B.1 Hydrogen-315,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl PK [sub Amino (nitroamino) methyl] amino] butyl]-(3.1 g, 5.48 mmol), carefully dissolved in 20 ml of HC1 37% under nitrogen at 0 ° C; so that the formed The mixture was warmed to room temperature and stirred overnight. The reaction mixture was washed with Et20 until the pinanediol was completely removed; the aqueous solution was concentrated to dryness and dried in vacuo to give 1.82 g (4.93 mmol, yield 90%) of the title compound, which was used in the 95014 -92- 200529810 No further purification required. 1HNMR (DMS0 + D20 + TFA): 3e78 (m? LH); 3.19 (m52H); 3.09 (m5 1Η); 1.71 (m, 2H); 1.70-1.48 (m, 3H); 1.49-1.23 (m, 2H) ); 0.89 (d, J = 5.8 Hz, 3H); 0.88 (d, J = 5.8 Hz, 3H) · Example C.3 Synthesis of other intermediates The intermediates reported below start with the appropriate intermediates, and Prepared according to any of the procedures described in Example Cl: (2S, 3R) -2-amino-3-hydroxybutamidamine, N-[(1R) small [(3aS, 4S, 6S, 7aR) -six Hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl]-, hydrochloride

lHNMR (DMSO-d6) (5h: 8.62 (1H, d, J = 5.0 Hz); 8.17 (3H5 d3 J = 3.5); 4.28 (1H, dd, J = 8.8, 1.8); 3.78 (lH, m); 3.52 (lH, m); 3.00 (lH, m); 2.28 (lH, m); 2.10 (lH, m); 1.92 (lH, t, J = 5.7); 1.84 (lH, m); 1.75-1.62 ( 2H, m); 1.43 (lH, m); 1.31 (3H, s); 1.25 (3H, s); l_22 (lH, d, J = 10.6); 1.14 (3H, d, J = 6.2); 0.88 ( 3H, d, J = 6.4); 0.86 (3H, d, J = 6.4); 0.81 (3H, s). (2S) -2-amino ureidopentanamine, N-[(1R) small [ (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] Butyl]; hydrochloride 95014 • 93- 200529810 palmarity

CIH H2N

1H NMR (DMSO-d6) 8.51 (1H, d, J = 5.1 Hz); 8 · 17 (3H, br); 6.1 (1H, br); 4 · 27 (1H, dd, J = 8.6 Hz, 1 · 8); 3.73 (1H, m); 2.99 (1H, m); 2.94 (2H, t); 2.27 (1H, m); 2.10 (lH, m); 1.92 (lH, t, J = 5.5); 1.82 (1¾ m); 1.75-U5 (9H, m); 1.30 (3H, s); 1.23 (3H, m); 0.87 (3H, d, J = 6.0); 0.85 (3H, d, J = 6.0); 0.80 (3H, s). (2S) -2-Amino-3-aminomethylamidinopropylamine, N-[(lR) -l-[(3aS, 4S , 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane Base]; hydrochloride

Confrontation

1H-NMR (DMSO-d6): 8.46-8.41 (1H, m); 8.06 (3H, bs); 7.67 (1H, s); 7.26 (1H, s); 4.30-4.25 (1H, m ); 4.08-4.02 (1H, m); 2.96 (1H, m); 2.60-2 · 52 (lH, m); 2.36-2_24 (lH, m); 2.20-2.10 (lH, m) ; 1.95 (lH, t, J = 5_5); 1.88-1.83 (lH, m); 1.75-1.60 (2H, m); 1.46-1.36 (lH, m); 1.32 (3H, s); 1.30-U8 ( 6H, m); 0.86 (6H, t, J = 6.7); 0.82 (3H, s). 2-Aminoacetamidamine, team [(15,2 拗 -1-[[((1 汉) -1 -[(3 (18,48,68,7 (111) -hexahydro-3 (1,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] small methylbutane 95014 -94- 200529810 group]; hydrochloride

CIH ^ -NMRCDMSO-de): 8.50 (1H, s); 8.20 (3H5bs); 4.29 (1H, d5 J = 7.70 Hz); 3.15 (2H, bs); 3.05 (lH, s); 2.36-2.24 (lH , M); 2.20-2.10 (lH, m); 1.95 (1H, t, J = 5.38 Hz); 1.85 (1H, s); 1.75-1.60 (2H, m); 1.50-1.38 (1H, m ); 1.35-1.30 (3H, m); 1.28-1.25 (4H, m); 1.24-U7 (lH, m); 0.86 (6H, t, J = 5.94Hz); 0.84 (3H5s). Example C.4 (2S) -2-amino_3-[(4-methylbenzylidene) amino] propanamide, N-[(lR) -1 _ [(3aS, 4S, 6S, 7aR) · hexahydro _3a, 5,5_trimethyl-4,6-methylalkyl_1,3,2_benzodioxofluoren-2-yl] _3_methylbutyl]-, hydrochloride

(2S) -2-[(l, l-dimethylethoxycarbonyl) amino] -3-[(4-methylbenzyl) -amino] -propanilamine of Example B.4 , Team [(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-diamidino-4,6-methylalkyl-1,3,2 -Benzodioxofluoren-2-yl] -3-methylbutyl]-(740 mg, ι 65 mol, 1 equivalent), soluble in i, 4-dioxolane (2〇 Ml). To this solution, 4NHC1 (5 ml, 19.8 mmol, 12 eq.) In 1,4-dioxolane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure 95014 • 95- 200529810 to obtain 800 mg of a glassy solid (quantitative yield). ^ NMRCDMSO-d ^ S ^ Cl ^ d, J = 5.5Hz); 8.38 (1H? T5 J = 8.4 Hz); 8.34 (3H, br); 7.80 (2H, t, J = 8.2); 7.28 (2H, d, J = 8.2 Hz); 4.15 (1H, dd, J = 8.8, 1.8); 4.02 (lH, br); 3.66 (lH, m); 3.55 (lH, m); 2.99 (1¾ m); 2.35 ( 3H, s); 2.19 (1¾ m); 2.06 (lH, m); 1.86 (lH, t, J = 5.7); 1.80 (lH, m); 1.64 (2H, m); 1.41 (lH, m); 1.33-1.19 (2H, m); 1.27 (3H, s); 1.21 (3H, s); L16 (1H, d, J = 10.6); 0.82 (3H, d); 0.80 (3H, d); 0 · 78 (3H, s) · Example C.5 2-S_amino-3_ (hexamidineamino) -propanamide, N-[(lS) -l-[[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5_trimethyl_4,6_methylalkyl_1,3,2-benzobenzodioxo-2-yl] -3-methyl Butyl] amino] carbonyl], hydrochloride

Let 2-S-[(l, l-difluorenylethoxycarbonyl) amino] -3- (hexamethylamino) propanamine, N-[(lS) -l-[[ (lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride -2-yl] -3-methylbutyl] aminomethyl] (450 mg, 0.8 mmol, 1 equivalent), dissolved in 1,4-dioxolane (15 ml). To this solution, 4 N HC1 (2.45 ml, 0.98 mmol, 12 eq.) In 1,4-dioxolane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure to obtain 400 mg of a glassy solid. Yield was quantified. Analytical data: iHNMRpMSa ^) ·: 8.54 (1H, d, J = 5.3 Hz); 8.18 (3H, br); 7.74 (1H, t, J = 5.7); 4.29 (1H, dd, 95014 -96- 200529810 J = 1.8,8.8); 3.83 (lH, m); 3.40 (2H, m); 3.00 (lH, m); 2.29 (lH, m); 2.11 (lH, m); 2.08 (2H, t, J = 7.5); 1.93 (lH, t, J = 5.5); 1.84 (lH, m); 1.75-U5 (llH, m); 1.32 (3H, s); 1.24 (3H, s); 0.86 (3¾ d, J = 6.6); 0_84 (3H, d, J = 6.6); 0.81 (3H, s). Example C.6

2-S-Amino-3- (4-fluorosulfoamidoamino) propanamide, meaning [(18) -1 _ [[(111) -1- [心 8,48,68,7 &amp; _Hexahydro-33,5,5_trimethyl_4,6_methylalkyl_1,3,2-benzodioxofluoren-2-yl] _3_methylbutyl] amino] Radical

Let two of each of Example B · 6 [(1,1-Dimethylethoxycarbonyl) aminofluorosulfoamidoamino] propanamide, [[18) -1 _ [[(111) -1_ [(3 &amp; 8,48,63,7 &amp; 11) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 -Yl] -3-methylbutyl] aminomethyl] (0.7 g, 1.14 mmol, 1 eq), dissolved in 1, 4-dioxolane (20 ml). To this solution, 4 N HC1 (3.4 mL '13.68 mmol, 12 equivalents) in 1,4-dioxolane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure to obtain 440 mg of a white solid. Yield 71%. Analytical data: ^ NMR (DMSO-d6). C ^ h: 8.54 (1H, d, J = 5.5 Hz); 8.26 (3H5 br); 7.89 (3H, m); 7.48 (3H, t3 J = 8.8), 4.26 (lH, dd, J = 1.3, 8.6); 3.84 (lH, m); 3.06 (2H, m); 2.97 (lH, m); 95014 • 97 · 200529810 2.25 (lH, m); 2.03 (lH, m) m); 1.83 (2H5m); 1.64 (2H, m); 1.42 (lH, m); 1.35-1.15 (3H? m); 1.28 (3H? s); 1.22 (3H5s); 1.11 (1H? d5J = 10.8 ); 0.85 (6H, m); 0.80 (3H, s). Example C.7 2-S-amino-3- (3,4-dimethoxyphenylacetamido) propanamide , Meaning [(18) _1_ [[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5_trimethyl-4,6-methylalkyl-1,3,2_ Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl], hydrochloride

• Make each of [(1,1-difluorenylethoxycarbonyl) amino] -3- (3,4-dimethoxyphenylacetamidinyl) -propanidine in Example B.7 , N-[(1S) -1-[[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] (0.3 g, 0.47 mmol, 1 equivalent) soluble in ι, 4-dioxo Lupin (20 ml). To this solution, 4NHC1 (1.43 ml, 5.71 mmol, 12 equivalents) in 4-dioxolane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure, diethyl ether was added, and evaporated to give 230 mg of a white solid. The yield was 85%. Analytical data iHNMR (DMSO-d6) 8.57 (lH5br); 8.12 (3H5br); 7.91 (1H51, J = 5.7 Hz); 6.86 (2H? M); 95014 -98- 200529810 6.76 (lH, dd, J = 1.8,8.2); 4.26 (lH, brd, J = 7.3); 3.82 (lH, m); 3.72 (3Η, s); 3.71 (3H, s); 3.36 (2H, s) ; 3.34 (2H, m); 2.99 (1H, m); 2.26 (1H, m); 2.10 (1H5 m); 1.92 (1H, t, J = 5.3); 1.83 (1H, m); 1.67 (2H5 m ); 1.45-1.15 (3H, m); 1.31 (3H, s); 1.23 (3H, s); 0.86 (3H, d, J = 6_6); 0.84 (3H, d, J = 6.6); 0 · 80 (3H, s). Example C.8 2-S_amino_3_ (3-phenyl-ureido) -propanilamine,] ^ _ [(18) -1 _ [[(111) -1- [ (3aS, 4S, 6S / 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6 · methylalkyl-I, 3,2-benzodioxoporoxan-2-yl]- 3-methylbutyl] amino] several groups], hydrochloride

Let each of the two [(1,1-dimethylethoxycarbonyl) amino groups in Example B.8; 1-3- (3-phenylureidomethyl) propanylamine, meaning [(18) _1-[[ (111) -1-[(3 &amp; 8,43,63,7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane Wulinyl] methylbutyl] amino] carbonyl] (0.58 g '0.1 mmol, 1 equivalent) was dissolved in M.dioxolane (25 ml). To this solution, 4 n HC1 (3 ml, 12.1 halo, 12 equivalents) in 1,4-dioxolane was added, and the solution was stirred at room temperature overnight. The solvent was removed under reduced pressure, diethyl ether was added and evaporated to give 0.52 g of the desired product. Yield is 100%. Analytical data: ^ NMR (DMSO-d6). 95014 -99- 200529810: 8.82 (1H, s); 8.59 (1H, d, J = 5.7 Hz); 8.18 (3H, br); 7 · 40 (2H, d, J = 7.9); 7.22 (2H, t, J = 8.1); 6.90 (1H, t, J = 7.3); 6.31 (1H, t, J = 5.7); 4.26 (1H , Dd, J = 1.5,8.6); 3.89 (lH, m); 3.48 (lH, m); 3_36 (lH, m); 3.01 (lH, m); 2.24 (1H, m); 2.10 (lH , M); 1.92 (lH, t, J = 5.3); 1.82 (lH, m); 1.67 (2H, m); 1.50-1.15 (3H, m); 1.31 (3H, s); 1.21 (3H, s) ); 0.85 (3H, d, J = 6.6); 0.84 (3H, d, J = 6.6); 0.79 (3H, s). Example C.9 Synthesis of other compounds φ The following compounds can be obtained from Example B.9 The intermediate was started according to the procedures of Examples C.4-C · 8. C.9.1 2-S-Amino-3- (acetamido) -propanilamine, 1 ^ [(18) -1-[[(11〇-1-[(3 &amp; 8,48,63, 7 & 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl ] Amine] carbonyl], HC1 salt · —- — αΗ --------- • C.9.2 2-S-amino-3- (9-fluorenylmethyloxyaminemethyl) _Propanamide, N-[(lS) -H [(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorane -1,3,2-benzodioxofluoren-2-yl] _3-methylbutyl] amino] carbonyl], HC1 salt. ΑΗ Η2Νχ! ^^ ά) &lt; 〇S C.9.3 2-S-amino-3- (pentylmethyl) -propylamine, N-[(lS &gt; l-[[(lR &gt; l-[(3aS54S? 6S57aR &gt; ^ Si -3a, 5,5 · Trimethyl-4,6-methylalkyl_1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl], HC1 salt. __〇, η C.9.4 2-S-Amino_3- (methyl pyrolite yellow amine) -propionic acid amine, called (13) -1-[[(111) -1-[(3 &amp; 3,43,63 , 7311) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo-monooxo-2-yl] -3-methylbutyl [Amine] carbonyl], HC1 salt. ----. In 0 _______— ^ 95014 -100- 200529810 C.9.5 2-S- 3--3-((ethoxycarbonylsuccinyl) -amidino] ethyl]-) propanil, N-[(lS) l · [[(lR) -1-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 · methylbutyl] amine Carbonyl], HC1 salt. C, H \ η κχ ~ f 0 C.9.6 2-S-amino-3- (wordoxyamine methyl) -propylamine, N-[(lS)- l-[[(lR) -l-[(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Boron-2-yl] -3-methylbutyl] amino] carbonyl], HC1 salt · cih \ η d ... C.9.7 3- [2- (1H-pyrazole): *] _ N -[(1S) -1-[[[((1R) -1-[(3 &amp; 3 ^, 63,7 &amp; 11) -hexahydro-3otrimethyl-4,6-methylalkyl-1, 3,2 · Benzodioxofluoren-2-yl-]-3-fluorenylbutyl] amino group], HC1 salt · C, H H2NV ^ NX ^ o / N5 ^ Example Dl Decdecylamine , Meaning [(18) -1-[[[(111) -1-[(328,48,68,7Note 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] 4-[[imino (nitroamino) methyl] amine Butyl]-

To a solution of decanoic acid (0.84 g, 4.83 mmol) in anhydrous DMF (30 ml), HATU (1.84 g, 4.83 mmol) and HOAt (0.66 g, 4.83 mmol) were added. After stirring at room temperature for 15 minutes, the mixture was cooled at 0 ° C. and N-fluorenylmorpholine (1-33 liters, 12.1 mmol) was added. After another 20 minutes, add (2S) _2-amino-5 · [[imine (wallylamino) fluorenyl] amino] amylamine] amylamine of Example C_1, 1 ^-[(111) -1_ [ (3 &amp; 8,48,68,7 &amp; 11) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoborohydride- 2-yl] each methylbutyl] -hydrochloride (2.2 g, 4.03 95014 -101-200529810 mmol). The mixture was allowed to warm to room temperature and stirred for 5 hours. Then, it was diluted with ethyl acetate (150 ml), 2% citric acid solution (2 × 100 ml), 2% NaHC〇3 solution (2 × 100 ml). ) And 2% NaCl solution (2 × cc). The organic phase was dried over sodium sulfate and concentrated. The residue was purified by column chromatography and eluted with an 80/20 to 100/0 AcOEt / n-hexane mixture. The solid formed was triturated with diethyl ether, collected by filtration, and dried under vacuum to give 1.8 g of product (72% yield).

Melting point 89-94 ° C Calculated by elemental analysis: C 59.99% Η 9.26% Ν 13.54% Acoustic measurement C 59.47% Η 9.51% Ν 13.42% ^ NMRCDMSO-dg): 8.82 (1H, d, J = 2.7 Hz); 8.53 (lH5br); 7.99 (1H, d, J = 8_05); 7.88 (2H, br); 4.33 (lH, m); 4.08 (lH, dd, J = 1.6, 8.6); 3.14 (2Η, m ); 2.56 (lH, m); 2.20 (lH, m); 2.11 (2H, m); 2.01 (lH, m); 1.84 (lH, t, J = 5.7); 1.79 (lH, m); 1.74- 1.58 (3H, m); 1.57-1.39 (5H, m); 1.32 (lH, d, J = 9.9); 1.24 (19H, m); 0.85 (9H5 m); 0.80 (3H5 s). Take the example of Cl (2S) -2-amino-5-[[imino (nitroamino) methyl] amino]-#pentamidine, N-[(1R) small [(3 &amp; 3,48 Qiu, 7 &amp; 11) -Hydrogen_3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoΗpentafluoren-2-yl] -3- 曱Butyl] hydrochloride and other compounds starting with the appropriate end acids, basically according to the experimental procedures described above, are reported in Table D-1. 95014 102-200529810 Table D-l

Example number Structural chemical name and analytical data D.1.1 T \ ΗΧ ° ^ Χ Η A 0 Chemical name: 荇 -2-carboxyamidamine, N-[(lS) -l-[[[(lR) -H (3aS , 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-form Butyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.97 (1H, d, J = 2.8 Hz); 8.71 (1H, d, J = 8.0 Hz); 8.54 (1H, br); 8.50 (1H, s); 8.1-7.9 (4H, m); 7.85 (2H, br); 7.6 ( 2H, m); 4.63 (1H, m); 4.09 (1H, m); 3.20 (2H, m); 161 (1H, m); 2.20 (1H, m); 2.01 (1H, m); 1.9-1.2 (11H, m); 1.23 (3H, s); 1.21 (3H, s); 0.85 (6H, d, J = 6.6); 0.79 (3H, s). D.1.2 1 Palmarity η A 0, 0 Chemical name: 2-Pyridoxamine, N-[(1S) -H [[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Amine) fluorenyl] amino] butyl] -Analytical data: 1H-NMR (DMSO-d6): 9.18 (1H, d, J = 1.3 Hz); 8.89 (1H, d, J = 2.4); 8.8- 8.65 (3H, m): 8.5 (2H, br); 4.59 (1H, m); 4.15 (1H, dd, J = 1.8, 8.6); 3.14 (2H, m); 2.72 (1H, m); 2.20 (1H, m); 2.02 (1H , m); 1.9-1.2 (11H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, 2 d, 1 = 6.6); 0.79 (3H, s). D.1.3, Para palmitate οΛ Chemical name: 3- (1,3-diketo-1,3-dihydro-isoamido-2-yl) -propanamide, N-[(lS) -H [[( lR) -H (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2 -Yl] -3-methylbutyl] amino] carbonyl] _4 _ [[imino (nitroamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.79 (1H, br); 8.51 (1H, br); 8.44 (1H, d, J = 7.8 Hz); 8.2-7.6 (2H, br); 7.85 (4H, m); 4.30 (1H, m); 4.08 1H , dd, J = 1.8, 8.6); 3.78 (2H, t, J = 6.3); 3.11 (2H, m); 2.59 (3H, m); 2.20 (1H, m); 2.01 (1H, m); 1.9 -1.2 (11H, m); 1.23 (3H, s); 1.22 (3H, s); 0.84 (6H, d, J = 6.6); 0.80 (3H, s).

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D.1.4 I Para palmitic HA Chemical name: 4-Butylbenzamide, ^ 4 (岱) -1-[[[((11〇-1-[(3 &amp; 8,43,63,7311)- Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl ] 冰 [[Imine (acylamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMS0-d6): 8.93 (1H, d, J = 2.9 Hz); 8.51 (1H, br); 8.24 (1H, d, J = 7.8); 8.2-7.6 (2H, br); 7.86 (2H, d, J = 8.2); 7.29 (2H, d, J = 8.2); 4.56 (1H, m ); 4.07 1H, dd, J = 1.8, 8.6); 3.16 (2H, m); 2.63 (2H, t, 1 = 7.1); 2.57 (1H, dt, J = 2.5, 7.1); 2.20 (1H, m ); 2.01 (1H, m); 1.9-1.2 (15H, m); 1.23 (3H, s); 1.22 (3H, s); 0.90 (3H, d, J = 7.3); 0.84 (6H, d, J = 6.6); 0.80 (3H, s). D.1.5 O ^^ NH I ~ 々IH l + 〇 is 〇Chemical name: 3-[(l, l-dimethylethoxy) carbonylamino] benzene Formamidine, hydrazone [(18) small [[[((11〇-1-[(3 &amp; 3,43,63 &gt; 10-hexahydro-3a, 5,5-trimethyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] Amino] butyl] -Analytical data: 1H-NMR (DMSO- d6): 9.48 (1H, s); 8.88 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 8.42 (1H, d, J = 8.0); 7.6-8.4 (2H, br): 7.97 (1H, s); 7.55 (1H, dd, J = 7.8, 1.1); 7.47 (1H, d, J = 7.8); 7.34 (1H, t, J = 7.8); 4.55 (1H, m); 4.09 ( 1H, dd, J = 1.8, 8.6); 3.17 (2H, m); 2.60 (1H, dt, J = 2.9, 8.4); 2.20 (1H, m); 2.02 (1H, m); 1.9-1.2 (11H , m); 1.48 (9H, s); 1.23 (3H, s); 1.21 (3H, s); 0.85 (6H, d, J = 6.6); 0.80 (3H, s). D.1.6 I Palmarity , N ^^ ΝΗ Η -I 0 χ0 Chemical name: 2- (2-methoxyethoxy) acetamidamine, N-[(lS) -H [[(lR) -l-[(3aS, 4S , 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenyl Butyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl Analytical data: 1H-NMR (DMSO-d6): 8.74 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 8.2-7.4 (2H, br); 7.69 (1H, d, J = 8.6); 4.39 (1H, m); 4.12 (1H, dd, J = 1.8, 8.6) ; 3.91 (2H, s); 3.57 (2H, m); 3.46 (2H, t, J = 4.6); 3.26 (3H, s); 3.13 (2H, m); 2.63 (1H, m); 2.21 (1H , m); 2.03 (1H, m); 1.9-1.2 (11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.85 (3H, d, J = 6.6); 0.83 (3H, d, J = 6.6); 0.80 (3H, s).

95014 104- 200529810

D.1.7 D.1.8 D.1.9 95014

Chemical name: 2- [2- (2-methoxyethoxy) ethoxy] acetamidamine, meaning [(13) -1-[[[(111) 小 [(3 &amp; 3,48,63 , 7wang11) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane [Amino] amino] carbonyl H-[[Imine (nitroamino) methyl] amino] butyl Analytical data: 1H-NMR (DMSO-d6): 8.74 (1H, d, J = 2.8 Hz) ; 8.52 (1H, br); 8.2-7.6 (2H, br); 7.69 (1H, d, J = 8.6); 4.40 (1H, m); 4.11 (1H, dd, J = 1.8, 8.6); 3.91 ( 2H, s); 3.6-3.4 (8H, m); 3.23 (3H, s); 3.13 (2H, m); 2.63 (1H, m); 2.20 (1H, m); 2.02 (1H, m); 1.9 -1.2 (11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.84 (3H, d, J = 6.6); 0.83 (3H, d, J = 6.6); 0.79 (3H, s) ._ Chemical name: (E) -3- (ethoxycarbonyl) propenamide, N-[(lS) -H [[(lR)-^ [(3aS, 4S, 6S, 7aR) -hexahydro-3a , 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4 -[[Imine (seminylamino) methyl] amino] butyl] Analysis Data: 1H-NMR (DMSO-d6): 8.78 (1H, d, J = 8.6 Hz); 8.77 (1H, s ); 8.55 (1H, br); 8.3-7.6 (2H, br); 7.12 (1H, d, J = 15 .5); 6.58 (1H, d, J = 15.5); 4.45 (1H, m); 4.19 (2H, q, J = 7.1); 4.12 (1H, dd, J = 1.8, 8.6); 3.15 (2H, m); 2.63 (1H, dt, J = 3.3, 8.6); 2.21 (1H, m); 2.04 (1H, m); 1.9-1.2 (11H, m); 1.25 (3H, s); 1.24 (3H, t, 1 = 6.9); 1.23 (3H, s); 0.85 (3H, d, J = 6.6); 0.83 (3H, d, J = 6.6); 0.80 (3H, s) .___ Chemical name: 2-six Hydropyridine-1-yl-acetamidamine, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-fluorenyl-l, 3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] ice [[imino (nitro Methylamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.79 (1H, d, J = 1.8 Hz); 8.53 (1H, br); 8.3-7.5 (2H, br); 7.79 (1H, br); 4.37 (1H, m); 4.12 (1H, dd, J = 1.8, 8.6); 3.13 (2H, m); 2.87 (2H, br); 2.62 (1H, m) ; 2.36 (4H, m); 2.20 (1H, m); 2.03 (1H, m); 1.9-1.2 (17H, m); 1.24 (3H, s); 1.21 (3H, s); 0.83 (6H, d , J = 6.6); 0.79 (3H, s).

105- 200529810 D.1.10 .0 ^ η human r 〇 is. Chemical name: 4- (1-fluorenyl-hexamidine p-ratio-4-yl) -butanamine, 1 ^ &quot;-[(18) -1-[[[(111) 小 [(3 &amp; 3 , 48,68,7 玨 10-hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane Analytical] Amino] carbonyl H-[[Imine (songylamino) methyl] amino] butyl] Analytical data. 1H-NMR (DMSO-d6): 8.82 (1H, d, J = 2.7 Hz ); 8.51 (1H, br); 8.01 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 6.94 (1H, t, J = 5.8): 4.33 (1H, m); 4.07 ( 1H, dd, J = 1.8, 8.6); 3.13 (2H, m); 2.78 (2H, br); 2.68 (3H, br s); 2.55 (1H, m); 2.19 (1H, m); 2.10 (2H , t, J = 7.5); 2.00 (1H, m); 1.85-1.1 (22H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, 2 d, J = 6.6); 0.79 (3H, s). D.1.11 I Palmarity, N ^^ NΗ η A 0 Chemical name: 2-acetamido-acetamido, &gt; 1-[(18) 小 [[[((111 ) 小 [(3 &amp; 3,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-Difluorenyl-4,6-methylalanyl-1,3,2-benzodioxane Fluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: 1H-NMR (DMSO -d6): 8.67 (1H, d, J = 2.7 Hz); 8.51 (1H, br ); 8.14 (1H, t, J = 5.7); 8.08 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 4.34 (1H, m); 4.09 (1H, dd, J = 1.8 , 8.6); 3.68 (2H, m); 3.13 (2H, m); 2.56 (1H, m); 2.20 (1H, m); 2.01 (1H, m); 1.84 (3H, s); 1.85-1.2 ( 11H, m); 1.24 (3H, s); 1.21 (3H, s); 0.83 (6H, d, 1 = 6.6); 0.79 (3H, s).

The compounds reported in Table D-1A are in accordance with the procedure of Example D.1 above, and using the (2S) -2-amino-5-[[imino (nitroamino) methyl) of Example C.1 [Amino] amino] pentamidine, hydrazone [(111) -1-[(3 &amp; 8,48,63,73 p-hexahydro-3 \ 5,5-trifluorenyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] -hydrochloride and appropriate carboxylic acids as starting materials. 106- 95014 200529810

Table D-1A Example No. Structural chemical name and analysis data D.1.2 Chemical name: 6-benzenesulfonylaminohexamidine, ^ [(13) -1-[[[(1foot ) -1-[(3wang 3,43,63,7 &amp; 11) -hexahydro-3〇trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 -Yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (Azidoamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.83 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 7.97 (1H, d, J = 7.8 Hz); 8.2-7.6 (2H, br); 7.77 (2H, m); 7.65-7.5 (4H, m); 4.31 (1H, m); 4.05 (1H, dd, J = 1.8, 8.6); 3.12 (2H, m); 2.69 (2H, q, J = 7.0); 2.54 (1H, m) ; 2.20 (1H, m); 2.05 (2H, t, J = 7.5); 2.01 (1H, m); 1.85-1.1 (21H, m); 1.22 (3H, s); 1.21 (3H, s); 0.82 (6H, d, J = 6.6); 0.79 (3H, s). D.1.3 κ r 〇Α〇 Chemical name: 8- (ethanesulfonylamino) octylamine 3-[(13) 小 [ [[(11〇-1-[(3 &amp; 5,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2 -Benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl analysis data : 1H-NMR (DMSO-d6): 8.81 (1H, br s); 8.51 (1H, br); 7.98 (1H, d, J = 7.8 Hz); 8.3-7.5 (2H, br); 6.93 (1H, t, J = 5.7): 4.32 (1H, m); 4.06 (1H, dd, J = 1.8, 8.6); 3.13 (2H, m); 2.95 (2H, q, J = 7.3); 2.87 (2H, q, J = 6.7 ); 2.55 (1H, m); 2.19 (1H, m); 2.10 (2H, t, J = 7.0); 2.00 (1H, m); 1.85-1.1 (17H, m); 1.23 (3H, s); 1.21 (3H, s); 1.16 (3H, t, J = 7.3); 0.83 (6H, d, J = 6.6); 0.79 (3H, s). D.1.4 Η Τ 〇- · Ν々ο Chemical name: 6- (ethanesulfonylamino) hexamidine, N-[(lS) -1-[[[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5 , 5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4- [ [Imino (nitroamino) methyl] amino] butyl] Analytical data: lH-NMR (DMSO-d6): 8.83 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 8.00 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 6.94 (1H, t, J = 5.8): 4.32 (1H, m); 4.06 (1H, dd, J = 1.8, 8.6 ); 3.13 (2H, m); 2.95 (2H, q, J = 7.3); 2.87 (2H, q, J = 6.7); 2.55 (1H, m); 2.19 (1H, m); 2.10 (2H, t , J = 7.5); 2.00 (1H, m); 1.85-1.1 (17H, m); 1.24 (3H, s); 1.21 (3H, s); 1. 16 (3H, t, J = 7.5); 0.83 (6H, d, J = 6.6); 0.79 (3H, s).

Example D.2 10- (1,3-diketo_1,3-dihydro-isoindole-2_yl) _decylamine,] ^-[(18) -1 _ [[((1 拗-1- 95014 -107- 200529810 [(3 Note 8,48,68,7 &amp; 11) -Hexahydro-3 this, 5,5_trimethyl_4,6_methylalkyl_1,3,2_ Benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] _4 _ [[imino (sonylamino) methyl] amino] butyl]-;

Based on the 10- (1,3-diketo-1,3-dihydro-isoolden_2-φ) -decanoic acid (353 mg, U1 mmol) prepared according to Example G.1 at To a solution in anhydrous dichloromethane (10 ml) was added N-methylmorpholine (122 µl, U1 mmol). The mixture was allowed to cool to -15 ° C, and then isobutyl chloroformate (144 μl, 1.11 mmol) was slowly added. After 15 minutes, add (2S) -2-amino-5-[[imino (nitroamino) methyl] amino] pentamidine of Example cl, Ke (1 柯 -1 _ [(3 &amp; 3,43 phoenix 7 &amp; 11) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluorenyl_2_yl] _3_form Butyl] -hydrochloride (508 mg, 1.01 mmol) with other N-methylmorpholine (122 μl, U1 mmol). The reaction mixture was stirred at -15 to 10 ° 4 · Hour, then, concentrated to a small volume and separated between ethyl acetate (20 ml) and water (10 liters). The aqueous phase was further extracted with ethyl acetate (10 ml). Combined The organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in ethyl acetate (3 ml), and the solution was added dropwise to hexane (120 ml) while stirring at room temperature. The solid was collected by decantation and dried under vacuum (730 mg, 94%). 'HNMRCDMSO- ^): 8.81 (lH5d5J = 2.7Hz); 8.52 (1¾ br); 7.98 (1H5 d5 95014 -108- 200529810 J = 8.05); 7.88 (2H, br); 7.85 (4H, m); 4.34 (lH, m); 4.06 (1Η, dd, J = 7.1); 3.56 (2H, t , J = 7.14); 3.14 (2H, m); 2.55 (lH, m); 2.19 (lH, m); 2.10 (2H, t, J = 7_14); 2.0 (lH, m); 1.82 (lH, t , J = 5.7); 1-78 (lH, m); 1.73-1.35 (10H, m); l_31 (lH, d, J = 9.9); 1.24 (19H, m); 0.84 (9H, m); 0.79 (3H, s) · Other compounds made basically according to the above experimental procedures are reported in Table D-2. Table D-2

Example number Structural chemical name and analytical data D.2.1 I Palmarity w T 0 'Chemical name: 4- (fluorenyloxycarbonyl) butanamine, N-[(lS) -l-[[[(lR) -l -[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl ] -3-Aminobutyl] amino] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.79 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 8.04 (1H, d, J = 7.9 Hz); 8.3-7.5 (2H, br); 4.31 (1H, m); 4.07 (1H, dd, J = 1.8, 8.6); 3.57 (3H, s); 3.13 (2H, m); 2.55 (1H, m); 2.28 (2H, t, J = 7.7); 2.20 (1H, m); 2.28 ( 2H, t, J = 7.5); 2.01 (1H, m); 1.85-1.2 (13H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H, d, J = 6.6); 0.79 (3H, s). D.2.2 S-r r 〇-〜〇 Chemical name: 4- (1-butyl-hexafluoro p-ratio-4-yl) -butanamine, 1 ^-[(13) -1-[[[((111) 小 [(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3 ^, 5-triamido-4,6-amidinyl-1,3,2 -Benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (alkylamino) methyl] amino] butyl] analysis Data: 1H-NMR (DMSO-d6): 8.78 (1H, d, J = 2.7 Hz); 8.51 (1H, br); 7.97 (1H, d, J = 8.0 Hz); 8.3-7.5 (2H, br); 4.32 (1H, m); 4.07 (1H , dd, J = 1.8, 8.6); 3.13 (2H, m); 2.78 (2H, br d, J = 11.2); 2.55 (1H, m); 2.19 (3H, m); 2.09 (2H, t, J = 7.5); 2.00 (1H, m); 1.85-1.0 (26H, m); 1.23 (3H, s); 1.21 (3H, s); 0.85 (3H, t, J = 7.9); 0.83 (6H, 2 d, J = 6.6); 0.79 (3H, s). 95014 109- 200529810

Chemical name ·· 2-butoxyacetamidamine, N-[(lS) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (Nitroamino) fluorenyl] amino] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.74 (1H, d, J = 2.8 Hz); 8.51 (1H, br); 8.3-7.5 ( 2H, br); 7.61 (1H, d, J = 8.0); 4.39 (1H, m); 4.12 (1H, br d, J = 8.2); 3.85 (2H, s); 3.42 (2H, t, J = 6.4); 3.13 (2H, m); 2.64 (1H, m); 2.20 (1H, m); 2.03 (1H, m); 1.95-1.2 (15H, m); 1.24 (3H, s); 1.21 (3H , s); 0.87 (3H, t, J = 7.3); 0.83 (6H, d, J = 6.6); 0.79 (3H, s) ·

Other compounds' made according to the procedures reported in Example D.2. Above are reported in Table D-2A. The compound of Example D.2.6 is the 2-aminoacetamidamine from Example D.14, [(13) 小 [[((111) 小 [(3 &amp; 8,48,68,7311) _hexahydro- 3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] • amino] carbonyl] -4-[[Imine (Zoamino) methyl] -amino] -butyl], starting from the hydrochloride. The compounds of Examples D.2.7 and D.2.8 are 2-aminoacetamidamine prepared from Example C.3, N-[(1S, 2R) _1-[[[((1R) 小 [(3 &amp; 3,48 , 68,7 &amp;)-Hexahydro-3 &, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -1 -Methylbutyl]; hydrochloride. The compounds of Examples 2.9 and 2.10 were prepared from (2S) -2-amino-5-lunyl pentylamine of Example C.3, ^ &quot; [(1 化) -1-[(3 &amp; 8 , 48,68,7 &amp; foot) -Hexazine-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl]- 3-methylbutyl]; hydrochloride. 110- 95014 200529810

Table D-2A

Example No. Structure Chemical name and analytical data D.2.4 Person H. Λ can \ X, NANh H 90-々0 Chemical name: 12-[(1,1-dimethylethoxy) carbonylamino] dodecylamine, N-[(1S) -H [[ (1R) Small [(3 &amp; 3,43,63,7 &amp; Phenyl-hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3,2-benzodioxane Wuyuan-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] -Analytical data: lH NMR ( DMSO-d6) 8.81 (1H, d, J = 2.4); 8.52 (1H, br); 7.98 (1H, d, J = 8.05); 7.85 (2H, v. Br); 6.73 (1H, t, J = 5.3); 4.33 (1H, m); 4.07 (1H, d, J = 8.4); 3.14 (2H, m); 2.88 (2H, q, J = 6.6); 2.56 (1H, m); 2.19 (1H, m); 2.10 (2H, t, J = 7.1); 2.01 (1H, m); 1.83 (1H, t, J = 5.7); 1.78 (1H, m); 1.73-1.41 (8H, m); 1.36 ( 9H, s); 1.33-1.15 (25H, m); 0.84 (6H, d, J = 6.5); 0.80 (3H, s). D.2.5. Opposition, .People &gt; S ^ AN Meaning ◦ YrKD &lt; HL 〇 』公 〇 Chemical name: 4- (methoxycarbonyl) heptylamine, [(13) 小 [[[((111) -1-[(3 &amp; 3,43,63,7 冱 11)- Hexaargon-3 ^, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl ] Amine] butyl] Analytical data: 1H-NMR (DMSO-d6): 8.80 (1H, br s); 8.51 (1H, br); 7.98 (1H, d, J = 8.0 Hz); 8.3-7.5 ( 2H, br); 4.32 (1H, m); 4.06 (1H, br d, J = 8.4); 3.12 (2H, m); 2.55 (1H, m); 2.26 (2H, t, J = 7.3); 2.18 (1H, m); 2.09 (2H, t, J = 7.1); 2.01 (1H, m); 1.85-1.2 (19H, m); 1.23 (3H, s); 1.21 (3H, s); 0.83 (6H , d, J = 6.6); 0.79 (3H, s). D.2.6 1 For palmity. ~, &Quot; N ^^ ΝΗ Η 夂 〇 ^ 0 Chemical name: 2- [2- (2-methoxyethoxy) acetamido] acetamido, [[18) -1-[[ [(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexagon-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzene Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl Analytical data: lH -NMR (DMSO-d6): 8.71-8.68 (1H, m); 8.53 (1H, m); 8.15 (1H, d, J = 8.1); 8.10-7.60 (3H, m); 4.40-4.33 (1H, m); 4.13-4.08 (1H, m); 3.92 (2H, s); 3.82-3.78 (2H, m); 3.64-3.58 (2H, m); 3.52-3.46 (2H, m); 3.27 (3H, s); 2.62-2.56 (1H, m); 2.26-2.16 (1H, m); 2.08-2.00 (1H, m); 1.85 (1H, t, J = 5.5); 1.82-1.76 (1H, m); 1.72-1.60 (3H, m); 1.59-1.40 (4H, m); 1.32-1.26 (4H, m); 1.25 (3H, s); 1.22 (3H, s); 0.86-0.83 (6H, m); 0.81 (3H, s).

95014 111-200529810 D.2.7

Palmarity. Chemical name: _decylamine, N- [l-[[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl- 4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3 · methylbutyl] amino] M group] methyl] Analytical data · 1H-NMR ( DMSO-d6): 8.85 (1H, s); 8.11 (1H, t, J = 5.9); 4.07-4.03 (1H, m); 3.83-3.78 (2H, d, J = 6.4); 2.24-2.16 (1H , m); 2.11 (2H, t, J = 7.40); 2.05-1.95 (1H, m); 1.84 (lh, t, J = 5.6); 1.8M.75 (1H; m); 1.74-1.60 (2H , m); 1.54-1.45 (2H, m); 1.35-1.30 (1H, d, J = 10.1); 1.28-1.20 (21H, m); 0.90-0.84 (9H, m); 0.81 (3H, s) ._ D.2.8

. Ύ υυά palm sex

Chemical name: 2- [2- (2-Methoxyethoxy) ethoxy] acetamidinium, 汴 [1-[[[[(11〇-1-[(3 &amp; 3,43,63,7 &amp; 10-hexahydro-315,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amine Group] carbonyl] methyl] Analytical data: 1H-NMR (DMSO-d6): 8.81 (1H, m); 7.97 (1H, t, J = 6.0); 4.09-4.04 (1H, m); 3.93 (2H, s); 3.85 (2H, d, J = 6.0); 3.64-3.57 (2H, m); 3.57-3.50 (4H, m); 3.45-3.40 (2H, m); 3.23 (3H, s); 2.58- 2.52 (1H, m); 2.24-2.15 (1H, m); 2.05-1.97 (1H, m); 1.83 (1H, t, J = 5.6); 1.80-1.76 (1H, m); 1.72-1.58 (2H , m); 1.31 (1H, d, J = 10.1); 1.28-1.25 (2H, m); 1.23 (3H, s); 1.21 (3H, s); 0.86-0.82 (6H, m); 0.80 (3H , ill

D.2.9

, Palmyl chemical name: Decylamine, N-[(lS) -H [[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4 , 6-Methylalkyl-l, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -5-ureidopentyl]-D.2.10

I-Zero Chemical Name: 4-Butylbenzidine N-[(1S) -1-[[[((1R) 小 [(3aS, 4S, 63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-fluorenylalkyl 4,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -5-urea Pentyl]-

Example 1X3 11-Cyanoundecylamine, meaning [(18) -1 _ [[[(111) _1-[(3 Note 8, 48, 68, 7 New 11) -hexahydro-3 \ 5,5 -Trimethyl-4,6-methylalanyl-1,3,2-benzodioxocarbox-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Asia Amine (acylamino) methyl] amino] butyl]-95014 -112- 200529810

PS-carbodiimide (N-cyclohexylcarbodiimide_N, _propoxymethyl polystyrene, 769 mg, 丨 mmol, 131 mmol / g) and HAt (1-Hydroxy-7-nitrobenzotriazole, 115 mg, 0.85 mmol) was added to n-cyanoundecanoic acid (115 mg, 0.54 mmol) in methane (DCM) ) (9 ml). After stirring for 10 minutes, (2S) -2-amino group_5_ [[imino (sonylamino) methyl] amino] pentamidine, N_K1R) _1-[(3aS, 4s, 6S, 7aR) • Hexahydro_3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2_benzodioxofluoren-2-yl] _3_methylbutyl] -, Hydrochloride (251 mg, 0.50 mmol) with DIPEA (0.128 ml '0.75 mmol). This suspension was shaken at room temperature overnight, then the PS-carbodiimide was filtered off and the strips were washed several times with DCM (4 X 6 mL). The organic phase was passed through a VARIAN CHEM ELUT cartridge for liquid-liquid extraction, preconditioned with a saturated aqueous solution of NaHC03, and finally washed with DCM (15 mL). The solvent was evaporated and the crude reaction was purified on a normal phase ISOLUTE SPE-SI column (DCM 9, MeOH 1) to give 200 mg of the desired compound (yield 61%). NMR (CDC13): 7.53 (s, br , 2H); 7.36 (d, br, J = 4.7Hz, lH); 6.88 (d, J = 8.2 Hz51H); 4.46 (m, lH); 4.15 (dd, J = 8.5, 1.9 Hz? 1H); 3.19 (m? 2H); 2.93 (m, 1H); 2.23 (t, J = 7.2 Hz, 2H); 2.21 (m, 1H); 2_09 (t, J = 7.5, 2H); 2.04 (m, 1H); 1.88 (t, J = 5.4 Hz, 1H); 1_77 (m, 1H); 1.69 (m, 1H); 1.64-1.43 (m, 9H); 1.40-1.26 (m, 4H); 1.26 (s, 3H) ; 1.24_1.12 (m, 16H); 0.80 (d, 95014 -113- 200529810 J = 6.6, 3H); 0.79 (d, J = 6.6, 3H); 0.73 (s, 3H). LC-MS 659.7, MH + .ESIPOS; AQA; spray 4kV / demister: 20V / probe 250 C. Other compounds made basically according to the above experimental procedures are reported in Table D-3. Table D-3

Example number Structural chemical name and analysis data D.3.1 Chemical name: Decylamine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodilactone sulfan-2-yl] -3-fluorenylbutyl] amino] several groups]- 4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 621.5 D.3.2 I Palmarity 〇_〜〇 Chemical name: Naphthalene small carboxamide, N -[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (acylamino) fluorenyl] amino] butyl Analytical data: MS: MH + 621.4 D.3.3 | Palmar H 〇A0 Chemical name: 2-phenylacetamidamine, N-[(lS) -l-[[[(lR) -l-[( 3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3 -Methylbutyl] amino] carbonyl] -4-[[Imine (acylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 585.3 D.3.4 Palmarity, N ^ ^ ΝΗ Η U 〇Chemical name: 1-phenylcyclopentanecarboxamide ^ H (lS) -l·l [[(lRl·l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1, 3,2-benzodioxo-2-enyl] -3-fluorenylbutyl] amino] carbonyl] dong [[imino (acylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 639.4 95014 114-200529810 D.3.5. Palmarity OVNH々 ^ x H lt o_ ~. Chemical name: (2R) -2-phenylbutyramine, N-[(lS) small [[[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Boroline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 613.4 D.3.6 I shift each Η l + o to palmity 0V. Chemical name: (2S) -2-phenylbutyramine, N-[(lS) -H [[(lR) 小 [(3aS , 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-form Butyl] amino] carbonyl] ice [[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 613.4 D.3.7 Antipodal, meaning r 〆〇 Chemical name : Dodecylamine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7 aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amine [Amino] carbonyl] · 4-[[Imino (sodiumamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 649.5 D.3.8 I Paramethylene-Η 〇 \ Chemical Name: Octyl Amine, N-[(lS) -l-[[[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl- 1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino ] Butyl] Analytical data: MS: MH + 593.4 D.3.9 Palmarity, N ^^ NΗ Chemical name: Acetylamine, N-[(lS) -H [[(lR) -l-[(3aS , 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-form Butyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 509.3 D.3.10 Η 〇Λ Chemical name: 4- (1,1-Difluorenylethyl) cyclohexanecarboxamide, N-[(1S) -1-[[((1foot) 小 [(3 &amp; 3,43,68,7 &amp; 11)- Hexaargon-3o-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl [Methenyl] Ice [[Iminino (stoneshothylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 633.5

95014 115- 200529810

D.3.11, The chemical name of palmar HL: trans-4-pentylcyclohexanecarboxamide, N-[(1S) -1-[[[(1R) 小 [(3 &amp; 3,43,63 , 7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3-methyl Butyl] amino] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data · MS ·· MH + 647.5 D.3.12 1 Palm HOK Chemical name : 4-phenylbutamidamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-l, 3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitro Amino) methyl] Amino] butyl] Analytical data: MS: MH + 613.4 D.3.13 I Para-HcA Chemical name: 2- (3-methoxyphenyl) acetamidamine, hydrazone [(13) -1-[[[((111) 小 [(三 旺 3,43,63,7 &amp; 11) -hexahydro-3 \ 5,5-trimethyl-4,6-fluoranyl-1,3, 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 615.3 D.3.14 h L 〇 』々〇 Chemical name: 4- (1,1-dimethylethyl) benzamide [[(13) 小 [[[((11〇-1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-3otrimethyl-4,6-fluoranyl-1,3 , 2-Benzodioxoborohydrin-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamino) methyl] amino] butyl] analysis Data · MS: MH + 627.5 D.3.15 | In the palm of hand, human r 〇- ~ Chemical name: Nonamidine, N-[(1S) 小 [[[((lR) -H (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] Amine] carbonyl] _4 _ [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 607.4 D.3.16 Η l + ο- ^ ο Chemical name: (RS)- 2-cyclopentylhexylamine, Hugh [(13) 小 [[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3〇trimethyl-4, 6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[Imine (acylamino) Fluorenyl] amino] butyl] Analytical data: MS: MH + 633.5 95014 116- 200529810

D.3.17 D.3.18 D.3.19 D.3.20 D.3.21 D.3.22 95014 For palm, \ x, for grip

_々0

0 ~ &gt; 0 Palmarium Palmarium Chemical Name: Benzene-2-carboxamide, meaning [(13) 小 [[[(111) 小 [(3aS, 4S, 6S, 7aR) -hexagon- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4 -[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 577.2 Chemical name: 2,3-difluorobenzamide, &gt; ^ [(18)- 1-[[[((111) 小 [(3 &amp; 3,48,63,7311) -hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2- Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data : MS: MH + 607.3 Chemical name: 2- (2-iodophenyl) acetamidamine, [(13) -1-[[[(111) -1-[(3 &amp; 3,45,63,7mad 11) -Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine [Amino] carbonyl] -4-[[Imine (acylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 711.3 \, and

NH A

〇 ^ 0 Palmarity Palmarium 117- Chemical name: Cyclohexanecarboxamide, 乂 [(13) 小 [[[(11〇-1-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4 -[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 577.3 Chemical name: 2- (4-bromophenyl) acetamidamine, [[13)- 1-[[[(1 foot) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trismidin-4,6-fluoranyl-1,3,2- Benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data MS: MH + 663.2 Chemical name: benzamidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5 -Trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[Asia Amino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 571.3 200529810

Chemical name: 2-methylbenzidine, N _ [(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Amino) methyl] amino] butyl] Analytical data: D.3.24 D.3.25 D.3.26

Confrontation

Palmarity D.3.28

MS: MH + 585.3 Chemical name: 4-bromobenzylamine, meaning [(13) -1-[[[(1foot) -1-[(3 &amp; 3,48,63,7 &amp; foot)-6) Hydrogen-3,5,5-trimethyl4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] Winter [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 649.3 Chemical name: (2S) -2-phenylpropanamide, N-[(lS) small [[[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3,2-benzobis Oxoborohydrin-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (Zoamino) methyl] Amino] butyl] Analytical data: MS : MH + 599.3 Chemical name: (E) -2-fluorenyl-3-phenyl-acrylamide, Qin [(13) -1-[[[(111) 小 [(333,43,65,7 王 11 ) -Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2 · benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 611.4 Chemical name: 2-[(naphthalene-2-yl) oxy] acetamidamine, meaning [(13) -1-[[((1foot) -1-[(3 &amp; 8,45,68,7hex11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6- Methyl-1,3,2-benzene Benzodioxo-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (sonylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 651.4_ Chemical name: 2,2-Difluorenylbutanamine, Qin [(13) -1-[[[(111) -1-[(3wang3,43,63,7 &amp; 1 〇-Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino ] Amine] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 565.4 95014 118- 200529810

D.3.29 I Palmitic 0ΤΎ shift% η human r o '^^ o Chemical name: 2- (2-Gaphenyl) acetamidamine, N-[(1S) -H [[(1R) -1- [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl]- 3-Methenylbutyl] amino] carbonyl] -4-[[Imino (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 619.3 D.3.30 I Palmar NjlH 〇_ ～ 〇Chemical name: 5-methylpyridine-2-carboxamide, 1 ^ [(13) 小 [[[(111) 小 [(3 汪 8,48,63,7 &amp; 1〇- 六Hydrogen-3otrimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4_ [ [Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 591.3 D.3.31 1 Palmar j ', NH 〇 &quot; ^^ 〇 Chemical name: cis-3 · (2-fluoroxyphenyl) acrylamide, hydrazine [(13) small [[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3 , 5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4- [ [Imino (sodiumamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 627.4 D.3.32 Palmarity 〇Human chemical name: (2-fluorenylphenoxy) acetamide, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl [[亚Amino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 615.4 D.3.33. • Palmarity ^ N * ^ ΝΗ ο '^^ ο Chemical Name: 2- (2, 5-Difluorenylphenyl) acetamidamine, 汴 [(岱) 小 [[[((11〇-1-[(3 &amp; 3,48,63,7 & 10-hexahydro-3 \: 5, 5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (Songylamino) methyl] amino] butyl] Analytical data MS: MH + 613.4 D.3.34 1 to 1M ± H. Chemical name: trans-3- (2-bromophenyl) acrylamide, &gt; ^-[(13) -1- [[[(111) 小 [(3 汪 3,43,68,7 汪 11) -hexaargon-3 &amp;, 5,5-trimethyl-4,6 -Fluorenyl-1,3,2-benzodioxo-2-enyl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) Fluorenyl] amino] butyl] Analytical data: MS: MH + 675.3 95014 119- 200529810 D.3.35

Parapetal o_々〇 Chemical name: 4-isopropylbenzidine, 1 ^ [(13) -1-[[[(111) -1-[(3 &amp; 8,43,63,7 &amp; 10-hexahydro-3, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] -4-[[Imine (acylamino) f-based] amino] butyl] Analytical data: MS: MH + 613.4 D.3.36 Opposition \ .χ.%: ΝΗ Λ 丨, Η 0 Chemical name: 4- (4-fluorenylphenyl) butanamine, 沭 [(13) -1-[[[(11〇 小 [(3 &amp; 8,43,63,7 &amp; 11)- Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl H-[[ Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 627.4 D.3.37 COlsy ^ NhI ^ Palmitic chemical name: 2- (2-fluorenylthio) acetamidine Amine, 汴 [(13) -1-[[[(11〇-1-[(3 &amp; 3,4,68,7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4, 6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (acylamino) ) Fluorenyl] amino] butyl] Analytical data: MS: MH + 667.3 D.3.38

The chemical name of palmity: 5-methylhexamidine, &gt; ^ [(13) -1-[[[(111) -1-[(3 &amp; 8,43,63,7 &amp; 11) -hexagon -315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4- [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 579.4 D.3.39 Palmarity

Chemical name: 3-pyrimidin-2-yl-propanilamine, N-[(1S) -H [[(1R &gt; 1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 -Trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[Asia Amine (wallylamino) methyl] amino] butyl] Analytical data: MS: MH + 605.4 D.3.40 Palmarity 0 \ x NH〇 Human chemical name: 2,4-dimethyloxazole-5 -Carboxamide, &gt; ^-[(13) -1-[[[(111) 小 [(3 &amp; 3,43,63,7 狂 11) -hexahydro-30,5-trimethyl-4 , 6-Amidino-1,3,2-benzodioxo-2-enyl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamino) Methyl] amino] butyl] Analytical data: MS: MH + 606.4 95014 120- 200529810

D.3.41 D.3.42 D.3.43 D.3.44 D.3.45 D.3.46 95014 Palmarity \, x, O '

121-Chemical name: Furan-3-carboxamide, N-[(1S) -1-[[[(1R) -1-[(3Wang 3,43,63,7 Madness) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] ice [[ Iminodi (methylamino) methyl] amino] butyl] Analytical data: MS: MH + 561.3 Chemical name: (2R) -2-phenylpropanamide, N-[(1S) _1-[[ [(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 599.4 Chemistry Name: 2-Cycloheptylacetamide, &gt; ^ [(13) 小 [[[(111) -1-[(3 巳 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5 , 5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imine (Aminoamino) methyl] amino] butyl] Analytical data: MS: MH + 605.4 Chemical name: 1-methylcyclopropanecarboxamide, &gt; ^ [(13) -1-[[[(( 11〇-1-[(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3〇trimethyl-4,6-pyridine-1,3,2-benzodioxin -2-yl] -3- Methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 549.3 Chemical name: 1-methyl-cyclohexyl Alkylcarboxamide, 怍 [(13) 小 [[[((1! 〇-1-[(3 &amp; 3,4168 &gt; !! 1) -hexahydro-3 &amp;, 5,5-trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (acylamino) methyl] Amino] butyl] Analytical data: MS: MH + 591.3_ Chemical name: 2-[(lS, 2R, 5S) -2-isopropyl-5-methylcyclohexyl] oxyacetamidamine, N- [ (lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxo-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 663.3 200529810

D.3.47 I Palmar Njh H o- ^ o Chemical name: (E) -2-Butene amine, meaning [(13) -1-[[[((11〇-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 535.6 D.3.48 I Para Si Si r 〇-N々 o Chemical name: 3-Methylbutyramine, [[18) -1-[[[(1 foot) -1-[(3 &amp; 3,43,63,7 &amp; 1〇-hexahydro-3〇 Trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (Nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 551.3 D.3.49 I Paraphysical 0_.々0 Chemical Name: 3-phenylpropanamide, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzene Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 599.3 D.3.50 palmar, xr ^ d κ human r Chemical name: 4- (4-methoxyphenyl) -butanidine, co-[(1 3) Small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) 4 hydrogen-30,5-trismidino-4,6-methylalkyl-1,3,2-benzodioxy Boroline-2-yl] -3-methylbutyl] amino] carbonyl H-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 643.4 D .3.51 I palmar κ human r Chemical name: iodophen-3-carboxamide, meaning [(13) 小 [[[((111) -1-[(3 压 3,43,68,7 &amp; 11) -Hexahydro-33,5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino ] Carbonyl H-[[Imino (acylamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 577.2 D.3.52 1 Opaque H. Human chemical name: 2-fluoren-3 -Methylacetamide, [(13) -1-[[[(1foot) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3〇trimethyl-4 , 6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] dong [[imino (nitroamino) methyl [Amino] amino] butyl] Analytical data: MS: MH + 591.4 95014 122- 200529810 D.3.53 1 Para palmar κ human r 〇-〜〇 Chemical name: (E) -Penta-2,4-dienoic acid hydrazone Amine, Qin [(13) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ( Nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 547.3 D.3.54 H Human chemical name: 2- (4-isopropylphenoxy) acetamidamine, N-[(1S ) -1-[[[((1R) 小 [(3wang 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-Benzodioxoboran-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl ] Analytical data: MS: MH + 643.4 D.3.55 for palm Si human r 0 is. Chemical name: 2- (4-Ethylphenoxy) acetamidamine, [(13) -1-[[[(1feet) -1-[(3ug 3, 43, 68, 7 &amp; 11) -Hexahydro-33,5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino ] Carbonyl] -4-[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 629.4 D.3.56 Palmar Η 〇Λ Chemical name: (E) -2 -Methylhex-2-enoic acid amide, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5- Tris (4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (Nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 577.2 D.3.57 Palmitic Njh HU 0_Ν々0 Chemical name: 3- (3-methylphenyl) acrylamide, Meaning [(13) 小 [[[(111) -1-[(3 &amp; 8,43,63,7ug11) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitro'ylamino) methyl] amino] Butyl] Analytical data: MS: MH + 611.4 D.3.58 I To palm HU 〇 _.% Chemical name: 2-Adamantane-1-ylacetamidamine, meaning [(13) 小[[[(1foot) -1-[(3 &amp; 3,43,63,710-hexahydro-3 &amp;, 5,5-trisyl-4,6-fluoranyl-1,3 , 2-benzodioxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl ] Analytical data. MS: MH + 643.3 123- 95014 200529810 D.3.59 I Palmarity h L o is. Chemical name: (RS) -2-Cyclopent-2-enylacetamidamine, bucket [(13) 小[[[(111) -1-[(3 冱 3,48,63,7 &amp; foot) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2- Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imino (acylamino) methyl] amino] butyl] Analytical data : MS: MH + 575.3 D.3.60 \. Palmarity ο '· Ν ^ ο Chemical Name: 4-Diethylaminobenzidine, N-[(1S) -1-[[[((1R) -1 -[(3aS, 4S, 6S, 7aR) -AlL-3a, 5,5-SfS-4,6-T alkyl-1,3,2-benzodioxoline-2-yl] -3 -Fluorenylbutyl] amino] carbonyl] -4-[[imino (canylamino) methyl] amino] butyl] Analytical data: MS: MH + 642.4 D.3.61 1 palmity, N ^^ NΗ HL 〇-, Chemical name: (RS) -2-Methylbutyramine, [[岱] -1-[[[(11〇-1-[(3aS, 4S, 6S, 7aR)- six Hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4 · [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 551.3 D.3.62 Para palmitic HL Chemical name: 3- (4-methylphenyl) Acrylamide, team [(18) small [[[(1 foot) -1-[(3 &amp; 3,43,63 &gt; 1〇-hexahydro-3〇trimethyl-4,6-methylalkyl-1 , 3,2-benzodioxobenzo-2-yl] -3-fluorenylbutyl] amino] carbonyl] dong [[imino (nitroamino) methyl] amino] butyl ] Analytical data: MS: MH + 611.4 D.3.63 1 Palm Njh HU 〇 is 〇 Chemical name: Hexa-2,4-dienoic acid hydrazine, swimming [(13) -1-[[[(1 foot)) -1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline- 2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imine (acylamino) methyl] amino] butyl] Analytical data MS: MH + 561.5 D.3.64 HL 〇 is 〇 Chemical name: 4-pyrrole-1-yl-phenylhydrazine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -six Hydrogen-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3 -Fluorenylbutyl] fluorenyl] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 636.3 124- 95014 200529810

D.3.65 D.3.66 D.3.67 D.3.68 D.3.69 D.3.70 95014

Confrontation

Antagonistic chemical name: (E) -3- ^ phen-3-yl-acrylamidonium, [[13) -1-[[[((111) -l-[(3aS, 4S, 6S , 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodilactone-wooden-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (Amidylamino) methyl] Amine] butyl] Analytical data: MS: MH + 603.3 Chemical Name: Hept-2-enylamine, N-[( 1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2 -Benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] analysis Data: MS: MH + 577.3 \ χ. ΝΗto

Confrontation

Confrontation

Parapetal 125- Chemical Name: 2- (3,4-dimethylphenoxy) acetamidamine, [[13] 小 [[[((111) -1-[(3 &amp; 3,43,68 , 7 Wang Chi) -Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino ] Carbonyl] -4-[[Imino (nitroamino) methyl] amino] butyl] Analytical data. MS: MH + 629.3 Chemical name: Dec-9-enamidon, hydrazone [(13)- 1-[[[((111) -1-[(3 and 3,43,63,7 Zhuang 11) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (acylamino) fluorenyl] amino] butyl] analytical data : MS: MH + 619.3 Chemical name: (E) -Undec-2-enoic acid sulfonamide, meaning [(13) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl 4,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl ] -4-[[Imino (nitroamino) fluorenyl] amino] butyl] Analytical data MS: MH + 633.4 Chemical name: (E) -Dec-3-enoic acid hydrazine, N- [ (1S) -H [[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluoranyl-1,3,2 -Benzodioxine Wuyuan-2- [Methyl] -3-f-butylbutyl] amino] carbonyl H-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 619.4 200529810

D.3.71 D.3.72 D.3.73 D.3.74 D.3.75 D.3.76 95014 Palmarity \, x.

• NH K

Palmity

Confrontation

Antagonistic Antagonistic Chemical Name: 2,2-Difluorenyl-3- (2-methylpropenyl) -cyclopropanecarboxamide, Mu [(13) -1-[[[((111) -1 -[(3 &amp; 3,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline- 2-yl] -3-methylbutyl] amino] carbonyl] ice [[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 616.9 Chemical Name: 2- Methylcyclohexanecarboxamide, [(13) 小 [[[((1trans) -1-[(3 &amp; 3,4 &amp; 63,7 冱))-hexahydro-3〇trimethyl-4 , 6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamine Yl) fluorenyl] amino] butyl] Analytical data: MS: MH + 591.4 Chemical name: 5-cyclohexylpentamidine, &gt; 1-[(13) 小 [[[(1 尺) -1-[( 3Jiang 3,43,63,7 &amp; 11) -Hexahydro-3 \ 5,5-trimethyl-4,6-fluorinyl-1,3,2-benzodioxoline-2 [Methyl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 633.5 Chemical Name: 3- Ethoxycyclohexanecarboxamide, 汴 [(13) 小 [[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6 · fluorenyl · 1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4- [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 607.3 Chemical Name: (3R) -3,7-dimethyl-oct-6-enoic acid amine , 1 ^ [(13) -1-[[[(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-315,5-trisyl-4,6- 曱Alkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (acylamino) methyl] amine Analytical data] MS: MH + 619.4

\also

NH 126- Chemical name: 3-[(4-methylamido) thio] propanamidin, 1 ^ [(1 幻 -1-[[[(1 办 l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 659.3 200529810

D.3.77 I Chemical properties of palmitate HU o ': (3S) -3,7-dimethyl-oct-6-enoic acid hydrazone, team [(13) 小 [[[((11〇 小 [(3冱 3,43,63,7 &amp; 11) -Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-Amidinobutyl] amino] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 619.4 D.3.78 I &gt; Palm Sex—Each person. Chemical name: (RS) -4-ethyloctylamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] Carbonyl] Ice [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 621.4 D.3.79 FI Palmitic H Λ 0, 0 Chemical Name: 5-Fluoro- 2-methoxybenzamide, N-[(lS) -l-[[[(11〇-1-[(3ug 3,48,63,7 &amp; 11) -hexagon-3 \ 5, 5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[imine (Wallylamino) methyl] amino] butyl] Analytical data: MS: MH + 619.2 D.3.80 Palmarity, N ^^ NΗ Η Ι + ο is 0 Scientific name: 2- (4-Bromophenoxy) -acetamidamine, 乂 [(13) 小 [[[((111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4- [[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 679.6 D.3.81 I Palmarity, N * ^^ NΗ Η 1, 0_々0 Chemical name: 2- (1-methyl-1H-pyridin-3-yl) acetamidamine, N-[(1S) -1-[[[(1R) 小 [(3 &amp; 3,43,63,7 &amp; 11 ) -Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino ] Carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data · MS: MH + 638.3 D.3.82 1 To nature ^ n &lt; ^ Nsnh Η A Chemical name: Six Hydrogen-2,5-methylalkyl Shuangwuyuan-3a (lH) -carboxamide, swimming [(13) 小 [[[(11〇-1-[(3 and 3,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino ] It]] Ice [[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data MS: MH + 615.2

95014 127- 200529810

D.3.83 I anti-H-Nv O 'Chemical name: Bicyclo [2.2.1] heptane-2-carboxamide, meaning [(13) 小 [[[(111) 小 [(3 &amp; 3, 43,63,7 &amp; 10-hexahydro-3,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride] -3-form Analytical data: MS: MH + 589.2 D.3.84 1 Palmar HL 〇_〜〇 Chemistry Name: (RS) -2- (4-Gaphenyl) propanilamine, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro -3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imino (nitroamino) methyl] amino] butyl] Analytical data MS: MH + 633.6 D.3.85 ^ NΗ Η 〇Α0 Chemical name: (2S) -2-A Butanidine, meaning [(13) 小 [[[(111) -1-[(3ug 3,48,63,7 冱 11) -hexahydro-3 \ 5,5-trimethyl-4, 6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] kisyl] -4-[[Imine (canylamine (Methyl) amino] amino] butyl] Analytical data. MS: MH + 551.8 D.3.86 Human W, N ^^ NΗ 〇 〇Λ Chemical name: ( 4RS) -1-[(1,1-dimethylethoxy) carbonyl] -hexahydropyridine-4-carboxamide N-[(lS) -l-[[[((lR) -l-[( 3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3 -Methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 678.4 D.3.87 1 Palmarium U Eight chemical names: (RS) -4-methyloctylamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4- [[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data · MS: MH + 607.3 D.3.88 1 Para palmitate Η L 〇'Ν ^ ο Chemical Name: 2-Fluoro- 5-methylbenzamide, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl PK [imino (nitroamino) Methyl] amino] butyl] Analytical data: MS: MH + 603.2

95014 128- 200529810 D.3.89

Counterpart chemical name: 2- (Bicyclo [2.2.1] hept-2-yl) acetamidamine, meaning [(13) -1-[[[(111) 小 [(3 &amp; 3,43,63 , 7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3-methyl Butyl] amino] carbonyl] -4-[[Imine (canylamino) methyl] amino] butyl] Analytical data: MS: MH + 603.8 D.3.90

〇_.々〇 Pair palm chemical name: Cyclopropane Carboxamide, [[18) -1-[[[(1foot) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a , 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[[ Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 535.3 D.3.91 Palm X / 0

〇 ~ Chemical name: 4-ethoxybenzimidamine, meaning [(13) -1-[[[(1foot) 小 [(3UG 3,43,68,7 &amp; 11) -hexahydro-3 &amp;, 5,: 5-Trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imine (wallylamino) methyl] amino] butyl] Analytical data: MS: MH + 615.2 D.3.92 Palmarity

ο- Chemical name: (E) -3- (4-bromophenyl) acrylamide, meaning [(15) 小 [[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 1 〇-hexahydro-33,5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino ] Amino H-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 675.1 D.3.93 xoVt:

Parasitizing chemical name: (2S) -2- (6-methoxyoxynaphthalen-2-yl) -propanilamine, [[13] 小 [[[(爪) 小 [(3 略 43,68 &gt; Ruler) -Hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] Amine] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 679.3 D.3.94

Parapetal chemical name: 3-fluoro-4-methoxybenzamide, co-[(13) 小 [[[[(111) -1-[(3 &amp; 8,48,63,7 狂 1〇 -Hexahydro-33,5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino H-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 619.5 95014 129- 200529810 D.3.95 Palmarity \ x,

fcNH Chemical name: 4-Fluoro-3-methylbenzidine, 乂 [(13) 小 [[[(111) 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (Amino) methyl] amino] butyl] Analytical data MS: MH + 603.2 D.3.96

0- ^ 0 The chemical name of palmitate: ammonium non-2-enoate, 仏 [(13) -1-[[[(1foot) -1-[(3 旺 3,43,63,7 &amp; 11 ) -Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 605.3 D.3.97 Palmarity

Chemical name: (E) -3- (naphthalene-2-yl) acrylamidonium, hydrazone [(13) -1-[[[(11〇-1-[(3 狂 3,43,63,7 王 11 ) -Hexagon-315,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Analytical data of carbonyl H-[[imino (pyridylamino) methyl] amino] butyl]: MS: MH + 647.3 D.3.98 Palmarity \ x.

Chemical name: quinoline-2-carboxamidine, [(13) 小 [[[((11〇-1-[(3 玨 3,43,63,7) -4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamine ) Methyl] amino] butyl] Analytical dataMS: MH + 622.3 D.3.99

ο- 'Palm chemical name: 1- (4-methoxyphenyl) -cyclopropanecarboxamide, team [(13) 小 [[[((111) -1-[(3 &amp; 3,43,63 , 7 &amp; foot) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenyl Butyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 641.4 D.3.101

Chemical name of palmitate: 3-butenamidamine, &gt; ^ [(18) -1-[[[(1foot) -1-[(3aS, 4S, 6S, 7aR) -AlL-3a, 5, 5-5f; &amp; -4,61 alkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[ Amino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 535.0 95014 130- 200529810 D.3.102 I Parapetical chemical name: Tetradecanylamine, hydrazone [(13) 小[[[(11〇-1-[(3 &amp; 8,48,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2 -Benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] ice [[imino (alkylamino) fluorenyl] amino] butyl] Analysis Data · MS: MH + 677.3 D.3.103 1 Palmarity νη Τ 0- ~ Chemical name: 3- (1fluorene-pyridin-3-yl) -propanilamine, 怵 [(13) -1-[[[(1 幻-1-[(3 冱 3,43,63,7 said) -Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl 4,3,2-benzodioxoborohydride- 2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 638.2 D.3.104 For palmity \ ίΗ 0 is. Chemical name: 4-phenoxybutymidine, 乂 [(18) 小 [[[(1 幻-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluorene-2- [Alkyl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 628.9 D.3.105 (V ^^ k η r Chemical name: 5-keto-5-phenyl-pentamidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S , 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 641.1 D.3.106 1 Palm sysyf 乂 x HU 〇 is 〇Chemical name: (2RS) -1-((1,1-Difluorenylethoxy) carbonyl) -hexahydropyridine-2-carboxamide, hydrazine [(13) 小 [[[(111) -1-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 [Alkyl] -3-fluorenylbutyl] amino] quinyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 678.2 D.3.107 ( Parapetal HL 〇:% Chemical name: Pyridine-2-carboxamide, N-[(1S) -H [[(1R) -1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl ] · 4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 572.1 95014 -131-200529810 D.3.108 Palmarity

Chemical name: Pyridine-3-carboxamide, team [(13) 小 [[[((111) -1-[(3 冱 3,43,63,7 &amp; feet) -hexahydro-3 \ 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (Masterylamino) methyl] amino] butyl] Analytical dataMS: MH + 572.1 D.3.109 Palmarity

Chemical name: Pyridine-4-carboxamide, team [(13) -1-[[[(1 foot) small [(3 &amp; 3,43,63,7 &amp; 1〇-hexahydro-315,5-tri Fluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ( Nitroamino) Amino] Amine] Butyl] Analytical data: MS: MH + 572.5 D.3.110 Parachemical name: (2S) -1-((1,1-dimethylethoxy) carbonyl ) -Hexahydropyridine-2-carboxamide, 乂 [(13) -1-[[[(1feet) -1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl PK [imine (Nitroamino) fluorenyl] amino] butyl] Analytical data. MS: MH + 678.1

Opaque chemical name: (2R) -1-((1,1-Difluorenylethoxy) carbonyl) -hexahydropyridine-2-carboxamide J-KlSH-HKlRH-iXSaSySjSJaR) -hexahydro-3a , 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4- [[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 678.2 D.3.112 Parapetical chemical name: 3,3-dimethyl-butanidine, N- [(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3 , 2-Benzodioxoboran-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (trimethylamino) methyl] amino] butyl ] Analytical data: MS: MH + 565.0 D.3.113 Chemical name: 4-[(phenylamino) carbonyl] butanamide, N-[(1S) -1-[[[((1R) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 \ 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-Aminobutyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data MS: MH + 656.2 95014 -132- 200529810 D. 3.114 I Palmar o--N ^ o Chemical name: 2,2-dimethylpentanamine, team [(13) -1 -[[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 579.2 D.3.115 I Palladium 0 ^ HA Chemical name: 5-P secphen-2-yl-pentamidine, 沭 [(13) 小 [[[((111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl ] Amine] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 633.2 D.3.116 1 Para palmar chemical name: (3RS) -1-((1,1-Difluorenylethoxy) carbonyl) -hexahydropyridine-3-carboxamide, N-[(lS) -l-[[[((lR) -l-[(3aS , 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3- Fluorenylbutyl] amino] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: MH + 678.0 D.3.117 Opaque 0-rR ^ f% &lt; κΛγ Chemical name: 8-phenyl-octylamine, meaning [(13) -1-[[[(1 尺) -1-[(3 have 3,43,63,7wang11) -Hexahydro-3 \ 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino ] Carbonyl [[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 669.1 D.3.118 1 Para palmitic, N ^^ NΗ HA Chemical name: 3-[[( 1,1-Difluorenylethoxy) carbonyl] amino] propanamidin, meaning [(13) -1-[[[(1feet) -1-[(3ug 3,43,63,7 &amp; 10-hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] -4-[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 638.2 D.3.119 Antagonism-0 ^ 0 Chemical Name: Thirteen Alkylamine, &gt; ^ [(13) 小 [[[[(1 幻 -1-[(3 and 3,43,63,7 &amp; 1〇-hexahydro-3〇trimethyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (acylamino) methyl] amino ] Butyl] Analytical data: MS: MH + 663.3 133- 95014 200529810

D.3.120 I Palmarium (A Chemical name: succinimidine, pyrene [(13) -1-[[[(111) -1-[(3 &amp; 3,43,63 &gt; 1〇-hexahydro- 3,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl]- 4-[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 566.1 D.3.121 1 For awkward HL Chemical name: Pentamidine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2- Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] [[imino (nitroamino) methyl] amino] butyl] Analysis Data · MS : MH + 551.2 D.3.122 Palmar PJ NH 〇- ~ 0 Chemical name: [[[((9H-g-9-yl) methoxy] carbonyl] amino] butanylamine, meaning [(13) 小 [ [[(111) -1-[(3 &amp; 8,43,63,731〇-hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3,2-benzodioxy Boroline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 775.3 D.3.123., Para palmar \ anh H 〇Λ Chemical name: 2- (dimethylamino) acetamide, N- [ (1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) · hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (Amidylamino) fluorenyl] amino] butyl] analysis Data: MS: MH + 552.5 D.3.124 1 palladium, human r 〇 』々〇 Chemical name: 5- (4-fluorophenyl) -pentyl®, N-[(lS) -l-[[[( lR) -l-[(3 &amp; 3,43,63,711) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzobis Oxyborin-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data · MS: MH + 645.2 D.3.125 1 Para palmar octyl chemical name: 8-keto-8-phenyloctylamine, N-[(1S) -1-[[[((1R) 4-[(3 汪 3,43 , 68,7 &amp; 11) -hexahydro-33,5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorene Butyl] amino] carbonyl] -4-[[imino (acylamino) methyl] amino] butyl] Analytical data MS: MH + 683.1

95014 134- 200529810

D.3.126 I for palm fjlH H. Human chemical name: 4- (pyrimin-2-yl) butanamine, 醯 [(13) 小 [[[((11〇-1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro -3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data. MS: MH + 619.0 D.3.127 I Palmar HL o_ ~ o Chemical name: 5-keto-5 Heptaphen-2-yl) pentamidine, ^ [(13) -1-[[((1foot) 小 [(3 &amp; 3,43,68 &gt; 11) -hexahydro-3〇trimethyl -4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino Amine) Fluorenyl] Amine] Butyl] Analytical data: MS: MH + 647.1 D.3.128 Para-K-Kr Chemical Name: 2- (3-Gaphenyl) acetamidine, Qin [(13)- 1-[[[(111) -1-[(3 ug 8,43,63,7 &amp; 11) -hexaargon-3〇trifluorenyl-4,6-fluoranyl-1,3,2-benzene Hexa-2-dioxo-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (wallylamino) methyl] amino] butyl] Analytical data · MS: [MH] + 619.1 D.3.129 Palms 08. Chemical name: Undecanesulfonium hydrazone [(13) -1-[[((claw) -1-[(3 disorder 3,43,63,7 &amp; 1〇-hexahydro-3 &amp;, 5,5- Trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imine (Azylamino) methyl] amino] butyl] Analytical data: MS: [MH] + 635.2 D.3.130 I Para palm SAr 0′々0 Chemical name: 4-heptylbenzylamine, N -[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (Azidoamino) methyl] amino] butyl] analysis Data: MS: [MH] + 669.6 D.3.131 I Palmarity 0 ™ Vvn * xs * nh Η 1. Chemical name: 6-phenylhexamidine, 乂 [(18) 小 [[[(1 feet) Small [(3 &amp; 3,43,63,7 &amp; 11) -Hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxyborohydride-2- [Methyl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 641.5 95014 135 -200529810

D.3.132 | Palmar o '^^ o Chemical name: 5-phenylpentylamine, 乂 [(13) 小 [[[((111) -1-[(3 旺 3,43,63,7 &amp; 11) -Hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imino (alkylamino) methyl] amino] butyl] Analytical data: MS: [MH] + 627.5 D.3.133 1 p-Benzene H. -Eight chemical names: 10-Hydroxydecylamine, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] M group] -4-[[imine (Nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 637.7 D.3.134 For palm s, r r 0.8, 0 Chemical name: 5 · keto-5- ( 4-phenylhexahydropyracyl) pentamidine, 醯 [(18) -1-[[[(111) -1-[(3 &amp; 8,48,63,7 pressure 11) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4 -[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 725.4 D.3.135 Paramidine Ι Ι + 〇_〜〇 Chemical name: 2- ( 1Η-tetrazol-5-yl) acetamide, 怵 [(13) -1-[[[(111) -1-[(3wang3,43,63,7mad 11) -hexahydro-3mad , 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxo-2-yl] -3-fluorenylbutyl] amino] carbonyl H- [ [Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 577.0 D.3.136 Palm value 1 η Λ 0 Chemical name : 2- (tetrazol-1-yl) acetamidamine, &gt; 1-[(13) -1-[[[(111) -1-[(3 &amp; 3,48,63,7 &amp; 11)- Hexahydro-3 \ 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] Analytical data: MS: [MH] + 576.9 D.3.137 1 Palmitic acid V, Chemical name: 2- (Pyrimidine -2-ylthio) acetamidamine, N-[(1S) 4-[[[((lR) -1-[(3 &amp; 3,43,63,7, and 11) -hexahydro-3〇trifluorene Phenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] kisyl] -4-[[imino ( Nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 618.9 95014 136- 200529810

D.3.138 I Palmar H 1. 〇 is 〇 Chemical name: 3-methylthiopropylamidamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S , 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl H-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: [MH] + 569.4 D.3.139 1 Palmar Η ΪΓ ο- Chemical name: 3- (fluoren-2-ylthio) -propanamidin, meaning [(18) small [[[(111) -1-[(3 狂 3,48,68,7 &amp; foot) -hexahydro-3 〇Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (Analylamino) methyl] amino] butyl] Analytical data: MS: [MH] + 681.5 D.3.140 1 Para-HL Chemical name: 2-[(phenylmethyl) thio] ethyl Lamine, team [(13) 小 [[[(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 \ 5,5-trimethyl-4,6- Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl ] Amine] butyl] Analytical data: MS: [MH] + 631.5 D.3.141 Para palmitized NjlH Η (Λ〇 Chemical name: 6-keto Amidine, meaning [(13) -1-[[[(111) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1 , 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (acylamino) fluorenyl] amino] butyl ] Analytical data: MS: [MH] + 593.5 D.3.142 • SR 〇- ~ 0 Chemical name: 4- (4-Axanesulfonylphenyl) -4-ketobutylamidine, [ (15) -1-[[[((11〇-1-[(3 &amp; 3,43,63,731〇-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-Benzodioxoborohydrin-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamino) methyl] amino] butyl] Analytical data : MS: [MH] + 705.0 D.3.143 I Palmarity, n ^ Njh H. Human chemical name: (2S) -1-Ethyltetrahydropyrrole-2-carboxamide, 泎 [(13)- 1-[[[(11〇-1-[(3 &amp; 3,43,63,7 &amp; 11) -hexagon-3a, 5,5-trimethyl-4,6-fluoranyl-1,3 , 2-Benzodioxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (nitroamino) methyl] amino] butyl] analysis Data MS: [MH] + 605.9 95014 137- 200529810

D.3.144 D.3.145 D.3.146 D.3.147 D.3.148 D.3.149 95014 Palmarity \ .x.

• NH A

Palmarity

Parapetal chemical name: 3-hydroxy-2,2-dimethylpropanamide, N-[(1S) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzyldioxolium-2-yl] -3-methylbutyl] amino] Carbonyl] -4-[[Imino (t-amino) methyl] amino] butyl] Analytical data: MS: [MH] + 566.9 Chemical Name: 2-Ethylthioacetamidamine, N- [(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3 , 2-Benzodioxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl PK [imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 569.8 Chemical name: 3-ureidopropanamide, N-[(1S) -1-[[[(1R) -1-[(3 玨 3,48,6min 7〇11) -Hexahydro-3otrimethyl-4,6-fluorenyl-1,3,2-phenylhydradioxo-2-yl] -3-methylbutyl] amino] carbonyl]- Analytical data for 4-[[Iminino (stonesynamino) fluorenyl] amino] butyl]. MS: [MH] + 581.5 Chemical Name: 3-methoxypropanamide, N-[(1S)- 1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trisynyl-4,6-fluorenyl-1,3,2-benzene Dioxo-2-yl ] -3-Methylbutyl] amino] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [MH] + 552.9

P-benzene

138- Chemical name: 2-methylthioacetamidamine, [(13) 小 [[[(1 幻 -1-[(3 旺 3,43,63,7 &amp; foot) -hexahydro-33,5 , 5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[ Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 555.6 _ Chemical name: 3H-imidazole-4-carboxamidinium, hydrazone [(13) 小 [[ [(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxo Fluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl PK [imino (nitroamino) fluorenyl] amino] butyl] Analytical data MS: [MH] + 561.0 _ 200529810

D.3.150 D.3.151 D.3.152 D.3.154 D.3.155 95014

Counterpart chemical name: 7-keto-octylamine, N-[(1S) small [[[((111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (Nitroamino) methyl] amino] butyl] Analytical data MS: [MH] + 607.1 Chemical name: (E) -3- (ranazol-4-yl) acrylamide, &gt; 1 -[(13) -1-[[[(111) -1-[(3 &amp; 3,43,68,7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4,6- Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl ] Amine] Butyl] Analytical data: __MS: [MH] + 587.4 Chemical name of palmity ··

139- (RS) -tetrahydrofuran-3-carboxamide, co-[(13) 小 [[[[(1 幻 -1-[(3 玨 3,43,63,7))-hexahydro-3 \ 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Asia Amino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 565.3 Chemical Name: (E) -3- (2-foxyphenyl) acrylamide, team [ (13) Small [[[((111) -1-[(3 &amp; 3,43,63 &gt; 10-hexahydro-3otrisyl-4,6-methylalkyl-1,3,2-benzo Dioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS : [MH] + 627.7_ Chemical name: 2-ethoxyacetamidamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro -3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] Analytical data: MS: [MH] + 553.0 Chemical Name: 3-furan-2-yl-propanamide, N- [(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl 4,3, 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl [Amino] amino] carbonyl H-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [MH] + 589.5 200529810

D.3.156 D.3.157 D.3.158 D.3.159 D.3.160 D.3.161 95014

Parapetic p-phenylene chemical name: 3- (benzenesulfonyl) propanilamine, meaning [(13) 小 [[[(111) 小 [(3aS, 4S, 6S, 7aR &gt; hexahydro-3a, 5 , 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[ Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 663.0

Confrontation

O 'Chemical Name: 4-Aminesulfobutamidamine, [[18) 小 [[[((111) -1-[(3 汪 3,43,63,7 &amp; 11) -hexahydro-33, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4- [[Imine (nitroamino) methyl] amino] butyl] Analytical data. MS: [MH] + 615.8 Chemical name: (4S) -2-keto-1,3-pyrazolidine- 4-carboxamide, team [(18) -1-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -AlL-3a, 5,5-Sfyl-4,6-form Alkyl-1,3,2 · benzodioxol-2-yl] -3 · methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl ] Amine] Butyl] Analytical data: MS: [MH] + 595.8 p-phenyl-p-phenylene Chemical name: (2R) -1-ethylfluorenyltetrahydropyrrole-2-carboxamide, [[18] -1-[[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3otrimethyl-4,6-methylalkyl-1,3,2-benzene Dioxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl PK [imine (nitroamino) methyl] amino] butyl] Analytical data MS: [MH ] + 605.9

Counterpart 140- Chemical Name: 3-[(Ethylamino) methylthio] • Propanamide, [[13] -1-[[[(111) 小 [(3ug 8,43,63 , 7 &amp; 11) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3-methylbutane [Amino] amino] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 626.0_ Chemical Name: 6- (ethylamido Thio) hexamidine, 泎 [(13) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl [Amino] amino] butyl] Analytical data: MS: [MH] + 638.9 ___ 200529810

D.3.162 I Parity 〇- ·% Chemical name: 〇thiophene-2-sulfonyl) acetamidine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutan [Amino] Amino] carbonyl] Ice [[Imine (Amineamino) methyl] Amine] butyl] Analytical data: MS: [MH] + 655.0 D.3.163 I for each of νγ HL 〇 is 〇Chemical name: 4- (Ethylamino) butanidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro -3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 593.7 D.3.164 Palm H. Human chemical name: (2Z) -3- (propylaminocarbonyl) -2-propene [[[(1 foot) -1-[(3wang 3,43,68,7 &amp; 5〇-hexahydro-3〇 三Fluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino ( Nitroamino) Methyl] Amine] Butyl] Analytical data: MS: [MH] + 606.1 D.3.165 Paramethylene-, meaning r Chemical name: 3- (octylsulfonyl) propanilamine, Bucket [(13) 小 [[[(1foot) -1-[(3 and 3,43,68 &gt; 11) -hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-fluorenyl -1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamino) methyl] amino] Butyl] Analytical data: MS: [MH] + 699.29 D.3.166 1 Palm s human τη 〇-〜ο Chemical name: 3- (octylthio) propanamidin, meaning [(岱) -1- [[[(111) -1-[(3 &amp; 8,43,63,7 狂 11) -hexagon-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2 -Benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] analysis Data: MS: [MH] + 667.35 D.3.167 •. Palmar κ r 〇- ·% Chemical name: 2,2-dimethylhexamidine Amine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-oxane -1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (seminino) methyl] Amino] butyl] Analytical data: MS: [MH] + 593.65 95014 141- 200529810

D.3.168 | Palladium ο_ · Ν々ο Chemical Name: 6-Hydroxyhexamidine, 乂 [(13) 小 [[[((1feet) -1-[(3aS, 4S, 6S, 7aR) -six Hydrogen-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl H-[[Imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 581.16 D.3.169 I Palmitic HA Chemical name: Hexahydro-3a, 5, 5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[imine (Nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [MH] + 565.60 D.3.170 Para palmar B ^-% Chemical name: 5-ketohexamidine, team [(13) -1-[[[(11〇-1-[(3 pressure 3,43,63,7 &amp; 11) -hexahydro-3otrimethyl-4,6-methylalkyl-1,3 , 2-Benzodioxoborohydrin-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (nitroamino) methyl] amino] butyl] analysis Data: MS: [MH] + 579.17 D.3.171 Palmar cCy ^ iNHX ^ \ χΛΛΛ HU 〇- ~ Chemical name: benzothiazole-6-carboxamide, hydrazone [(13) -1-[[[(( 111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Fluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl M-[[imino (nitro Amino) methyl] amino] butyl] Analytical data: MS: [MH] + 628.70 D.3.172 | Parachemical Name: 3- (octyloxy) propyl KK, N-[(1S) -H [[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane Wuyuan-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH ] + 651.33 D.3.173 I Palmar HL 〇 is 〇 Chemical name: 2- (2-netyl-tetraaza? Pyrolo-1-yl) -ethyl amine, meaning [(13) 小 [[[(( 111) -1-[(3 &amp; 3,43,63,7 &amp; trans) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Boroline-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [ MH] + 592.75 95014 142- 200529810

D.3.174 I The chemical name of palmitate: benzamidine, N-[(1S, 2R) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a , 5,5-trimethyl · 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] jiki] -2 _Hydroxypropyl] Analytical data: MS: [MH] + 471.47 D.3.175 For palmity, one. Fly chemical name: 2- [2- (2-methoxyethoxy) ethoxy] acetamidamine, team [(13,211) -1-[[[((111) -1-[(3 &amp; 3, 43,63 &gt; 11) -hexahydro • 3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenyl Butyl] amino] carbonyl] -2-hydroxypropyl] Analytical data: MS: [MH] + 527.12 D.3.176 1 Parachemical name: 4-phenylbutyramine, team [(1 民 211) -1-[[[((111) -1-[(3 玨 3,4 &amp; 63,7 狂 11) -hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3 , 2-Benzodioxoborohydrin-2-yl] -3-methylbutyl] amino] Jinyl] -2-hydroxypropyl] Analytical data MS: [MH] + 513.10 D.3.177 I Parapetal chemical name: (4-methylphenoxy) acetamidamine, N-[(1S, 2R) -1-[[[((1R) -1-[(3wang 3,43,63,7 &amp; 11) -Hexahydro-3otrimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl ] Hydroxypropyl] Analytical data: MS: [MH] + 515.57 D.3.178 Palmitic chemical name: Hexamidine, N-[(1S, 2R) -1-[[[(1R) -1- [ (3 &amp; 8,43,63,7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl ] Amine] carbonyl] -2-hydroxypropyl] Analytical data: MS: [MH] + 465.40 D.3.179 1 Para palm chemical name: 4-butylphenylhydrazine, hydrazone [(13,21〇 小[[[(111) -1-[(3 &amp; 3,43,63,7 狂 11) -hexagon-3hexyl, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2 -Benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] Analytical data MS: [MH] + 527.16 D.3.180 I Palmarity Chemical name: hydrazone-2-carboxamide, N-[(1S, 2R) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluorenyl] -3-fluorenylbutyl] amino] carbonyl] donghydroxypropyl] Analytical data · MS : [MH] + 521.14 95014 143- 200529810 D.3.181 I Palmarium ™ Each HA chemical name: Hexylamine, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl] amino] carbonyl H-[[Imine (Amidinoamino) methyl] amino] butyl] Analytical data: MS: [MH] + 565.33 D.3.182 1 Palmarity, N * ^ NΗ Η A Chemical name: 2- (4- 曱 benzenesulfonyl) ethanamine, 泎[(18) -1-[[((111) -1-[(3wang 8,48,63 &gt; feet) -hexagon-3hex, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (trimethylamino) methyl] amino] butyl Analytical data: MS: [MH] + 663.30 D.3.183 Palmarium Η 0 Λ Chemical name: Heptamidine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 579.34 D.3.184. Palmarity χ χ Λ Name: 11- (Aminemethylamidino) undecylamine, 汴 [(13) 小 [[[(111) 小 [(3 玨 3,43,68,73 feet &gt; Hexa-33,5, 5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[ Imino (acylamino) fluorenyl] amino] butyl] Analytical data: MS: [MH] + 678.44 D.3.185 I Para palmar kappa r 0- ~ 0 Chemical name: 2- (benzenesulfonium ) Ethylamine ^ -KlSyi-UKlRM-CPaSASAS / ZaR) -Hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3, 2-benzodioxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] -4 · [[imino (acylamino) fluorenyl] amino] butyl] Analytical data: MS: [MH] + 649.28

Other compounds prepared according to Example D.3 above are reported in Table D-3A. 144- 95014 200529810

Table D-3A

Example No. Structure Chemical name and analytical data D.3.186 | Palmarity 〇 Ξ \ / 你 0 为。 Chemical name: 9-cyanononamidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Fluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl PK [imino (nitroamino ) Methyl] amino] butyl] Analytical data: MS: MH + 632.5 D.3.187 1 Palmarity &quot;-Η οΛ) Chemical name: 11-cyanoundecylamine, N-[(1S)- 1-[[[((1R) · l-[(3aS, 4S, 6S, 7aR &gt; hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] [[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: MH + 659.7; 1H-NMR (CDC13): 7.53 (s, br, 2H); 7.36 (d, br, J = 4.7 Hz, 1H); 6.88 (d, J = 8.2 Hz, 1H); 4.46 (m, 1H); 4.15 (dd, J = 8.5, 1.9 Hz, 1H); 3.19 (m, 2H); 2.93 (m, 1H); 2.23 (t, J = 7.2 Hz, 2H); 2.21 (m, 1H); 2.09 (t, J = 7.5, 2H); 2.04 (m, 1H); 1.88 (t, J = 5.4 Hz, 1H); 1.77 (m, 1H); 1.69 (m, 1H); 1.64-1.43 (m, 9H); 1.40 -1.26 (m, 4H); 1.26 (s, 3H); 1.24-1.12 (m, 16H); 0.80 (d, 1 = 6.6, 3H); 0.79 (d, J = 6.6, 3H); 0.73 (s, 3H). D.3.1 88 I pair of palms, each S, r 〇-〜〇 Chemical name: 6- (acetamido) hexamidine, hydration [(13) 小 [[[((1foot) -l-[(3aS , 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorene Butyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 622.3 D.3.189 1 to zero \ Eight chemical name: 12- (1,3-diketo-1,3-digas-isoacholin-2-yl) -dodecylamine, team [(13) -1-[[[(( 1 magic-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3,2-benzodioxoborohydride -2 · yl] -3-methylbutyl] amino] carbonyl PK [imino (nitroamino) methyl] amino] butyl] Analytical data: MS: [MH] + 794.42 95014 145- 200529810 D.3.190

Chemical name: 3- [4- (2-propyl) phenyl] propanamide, N-[(lS) small [[[((lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a , 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4- [[Imino (nitroamino) methyl] amino] butyl] Analysis Data:

MS: [M] H + 641.5_ Chemical name: 3- [4- (ethyl) phenyl] propanamide, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43 , 68,7 &amp; 11) -Hexahydro-3 &amp;, 5,5-Dimethyl-4,6-methylalanyl-1,3,2-benzodilactate-2-yl] -3 -Fluorenylbutyl] amino] kisyl] -4-[[imino (nitroamino) methyl] amino] butyl] Analytical data: D.3.192

HO

Ο

MS: [M] H + 627.7 Petrological name: 6-Hydroxyhexamidine, 泎 [(13) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexagon-3a , 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 · yl] -3-fluorenylbutyl] amino] carbonyl H-[[ Imino (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [M] H + 581.5 Example D.4 Fluoro-2-sulfonamide, N-[(lS) -l- [ [[(lR) -1-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl_4,6_methylalkyl-1,3,2-benzodioxane Wuyi-2-yl] -3-methylbutyl I amino group I carbonyl group] _4_ [丨 Imine group (acylamino) methyl] amino group] butyl]-

In Example C1, (2S) -2-amino-5-[[imino (sonylamino) fluorenyl] -amino] -pentanamine, N-[(1R) small [(3 &amp; 3 , 43,63,7 &amp; 11) _hexahydro-3 \ 5,5_trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl]- 3-methylbutyl]-, hydrochloride (70 mg, 95014 -146- 200529810 0.14 mmol) in DCM (4 ml), TEA (〇_〇4 ^: Liter '.31 millimoles) and gadolinium chloride 2-continuous thorium (351 mg, 016 millimoles). After stirring overnight, a second portion of TEA (4.0 ml, 031 mmol) and gasified tea-2-Ji (35.1 mg, 0.6 mmol) were added, and the reaction was stirred overnight . The reaction mixture was then washed with a saturated aqueous K2CO3 solution and the separated organic phase was concentrated to dryness. The crude reaction was purified on a SPE_SI normal phase cartridge to obtain the title compound (64 mg, 70% yield). NMR (CDC13): 8.42 (s, br5 1H); 7.96 (dd3 J = 7.5? 2.2 Hz5 1H); 7.95 (d, J = φ 8_5Hz, lH); 7.89 (d, br, J = 7.9Hz, lH) ; 7.81 (dd, J = 8.8, 1.9Hz, lH); 7.68- 7.57 (m, 2H); 7.23 (s, br, 2H); 6.23 (s, br, lH); 6.03 (d, J = 8.5Hz , LH); 4.19 (dd5 J = 9.13 2.2 Hz, 1H); 3.92 (s, br5 1H); 3.31 (m5 2H); 2.97 (m, 1H); 2.26 (m, 1H); 2.12 (m, 1H) ; 1.93 (t, J = 5.7 Hz, 1H); 1.90-1.68 (m5 6H); 1.30 (s, 3H); 1.28 (m, 1H); 1.25 (s, 3H); 1.06 (m, 4H); 0 · 79 (s, 3H); 0.58 (d, J = 9.4 Hz, 3H); 0.56 (d, J = 9.4 Hz, 3H). LC-MS 657.3, MH +, ESIPOS; AQA; spray 4kV / demister : 20V / probe 250 C · φ Other compounds made basically according to the above experimental procedures are reported in Table D-4. Table D-4 Example number Structural chemical name and analysis data D.4.1 I Palmar, human NH HA Chemical name: &quot;-Naphthalene-1-carbamine, N-[(lS) -l-[[[ (lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3 ^ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride · 2-Alkyl] Each methylbutyl] Amine] carbonyl] · [[Imine (nitroamino) methyl] amino] butyl] Analytical data: MS: ΜΗ + 657.3 95014 -147 -200529810

D.4.2 D.4.3 D.4.4 D.4.5 D.4.6 D.4.7 95014

Opposition 〇- 令 ο

Palmity

Confrontation

Counterpart chemical name: sulfan-2-sulfonamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Asia Amino (trioamino) methyl] amino] butyl] Analytical data: MS: MH + 657.3; 1H-NMR (CDC13): 8.42 (s, br, 1H); 7.96 (dd, J = 7.5, 2.2 Hz, 1H); 7.95 (d, J = 8.5 Hz, 1H); 7.89 (d, br, 1 = 1.9 Hz, 1H); 7.81 (dd, J = 8.8, 1.9 Hz, 1H); 7.68-7.57 (m , 2H); 7.23 (s br, 2H); 6.23 (s br, 1H); 6.03 (d, J = 8.5 Hz, 1H); 4.19 (dd, J = 9.1, 2.2 Hz, 1H); 3.92 (s, br, 1H); 3.31 (m, 2H); 2.97 (m, 1H); 2.26 (m, 1H); 2.12 (m, 1H); 1.93 (t, J = 5.7 Hz, 1H); 1.90-1.68 (m , 6H); 1.30 (s, 3H); 1.28 (m, 1H); 1.25 (s, 3H); 1.06 (m, 4H); 0.79 (s, 3H); 0.58 (d, J = 9.4 Hz, 3H) ; 0.56 (d, J-9.4 Hz, 3H) ._ Chemical name: Decane-1-sulfamethoxamine, 泎 [(13) 小 [[[((1feet) -1-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amine Group] carbonyl] 4-[[imino (nitroamino) fluorenyl] amino] butyl Analytical data: MS: MH + 671.4 Chemical name: Octanesulfonamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro -3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline_2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: MH + 643.4 Chemical name: benzylsulfonamide, N-[(lS) -l-[[[( lR) -H (3aS, 4S, 6S, 7aR &gt; ^ hydrogen-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoborohydrin-2- [Methyl] -3-methylbutyl] amino] carbonyl H-[[Imine (wallylamino) methyl] amino] butyl] Analytical data: MS: MH + 607.3 Chemical Name: 4-butoxy Benzylsulfonamide, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) · hexahydro-3a, 5,5-trifluorenyl-4, 6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl H-[[imino (acylamino)] [Amino] Amine] Butyl] Analytical data MS: [M + H] + 679.5_ Chemical name: 4-butyl-benzenesulfonamide, 乂 [(13) 小 [[[(111) -1- [ (3,3,43,63,7 玨 11) -Hexahydro-3 \ 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2 -Yl] -3-fluorenyl Butyl] amino] carbonyl] _4 _ [[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: ίΜ] Η + 663.5_ -148-

200529810 D.4.8 — i Chemical name: H Jif] 4-pentyl-benzenesulfonamide, N-[(lS) -l. [[[(LR) -l-[(3aS, 4S, 6S, 7aR) . ^ lL-3a, 5,5-X fluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluorenyl] -3-methyl, NΗ ΗL-butylbutyl] Amine] carbonyl] -4-[[Imine (nitroamino) fluorenyl] amino] butyl] Analytical data: MS: [M] H + 677.3 Example D.4.9 Fluoren-2-sulfonamide, Meaning [(18,211) _1-[[[(111) _1-[(338,48,68,7211) -hexagon-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino Icarbonyl] -2-hydroxypropyl]

Gasified osmium-2_sulfohydrazone (144 mg, 0.637 mmol) was added to the (2S) -amino- (3R) _hydroxy-butyric acid sulfonamide of Example C.3, N _ [(lS) -1 -[[[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl_4,6_methylalkyl-1,3,2-benzodioxy Boron-2-yl] -3-methylbutyl] amino] -carbonyl], hydrochloride and NMM (0-175 ml, 1.59 mmol) in a solution of anhydrous digas methane, at the same time, in 0 ° C and stirred under nitrogen. After 6 hours, the mixture was allowed to warm to room temperature and stirred overnight. 10% NaHC03 solution (10 ml) was added, and the layers were separated. The aqueous phase was further extracted with methane (5 ml). The organic phase was washed with a 20% NaH2P04 solution, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography (silica gel '25 g) and dissolved in a mixture of 1: 1 (v / v) hexane and ethyl acetate. The product was obtained as a white glassy solid (219 mg, 74% yield), but still contained some pinanediol. A sample (160 mg) of this product was triturated with a mixture of diethyl ether (3 ml) and hexane (3 ml). The pure product was obtained as white 95014 -149- 200529810.

Color solid (80 mg, 27% yield). Melting point 147-149 ° C. ^ NMRCDMSO- ^): 8.40 (1H5s); 8.28-8.22 (1H5 m); 8.11 (lH5d5J = 7 · 7); 8_05 (1H, d, J = 8.7); 8.01 (1H, d, J = 7.8); 7.81 (1H, dd, J = 8.7, 1 · 7); 7.75 (1H, s br.); 7.72-7 · 61 (2H, m); 4.84 (1H, s br.); 4.03 (1H, dd, J = 8.5, 1.7); 3.82-3.72 (2H, m); 2.41-2.33 (lH, m); 2.20-2.10 (lH, m); 2.02-1.93 (lH, m) ; 1.82-1.72 (2H, m); 1.58-1.50 (lH, m); 1.36-1.24 (lH, m); 1.20 (3H, s); 1_18 (3H, s); 0 · 99 (3H, J = 6.1); 0.94-0.82 (2H, m); 0.77 (3H, s); 0.63 (3H, d, J = 7.1); 0.61 (3H, d, J = 7.1). Example D.5 (2S) -4 _ [[Imine (songylamino) methyl] amino] _2-[(2-theylmethyl) _amino] -pentamidine, [[1拗 -1 _ [(338,48,68,7 &amp; 11) -hexaargon_3 &amp; 5,5-trimethyl_4,6-methylalkyl-1,3,2-benzodioxin -2-yl] -3-methylbutyl]

(2S) -2-Amino-5-[[imino (nitroamino) methyl] amino] pentamidine, N-[(1R) small [(333,43 Hydrazone, 7 &amp; 10-hexahydro-3o trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] -, A solution of the hydrochloride (88 mg, 0.175 mmol) in MeOH (4 ml), passed through an ISOLUTE PSA cartridge 'to obtain the starting material as a free base. The free base is in MeOH (4 ml In the solution in), add 2-hydrazaldehyde (45 mg, 0.28 mmol) and NaCNBH3 (18 mg, 0.28 mmol) at room temperature; add AcOH until the pH of the solution is 4-5. The reaction mixture was stirred overnight, then, 95014-150-200529810 Η20 (1 ml) was added, and the resulting solution was concentrated; the residue dissolved in AcOEt was washed with brine, and the organic phase was concentrated to dryness. Crude The reaction was purified by silica gel flash chromatography (DCM / MeOH / NH4OH, 97 · 5/2 · 5/0 · 25) to obtain the desired compound (30 mg, yield 28%).

NMR (CDC13 + D20): 7.81 (m, 3H); 7.71 (s, br, 1H); 7.52-7.38 (m, 3H); 4.66 (s, br, 1H); 4.27 (dd, J = 8.8, 1.9 Hz, 1H); 3.91 and 3.83 (Others 211); 3.39-3.11 (m53H); 2.30 (m? LH); 2.13 (m? 1H); 1.98-1.45 (m, 8H); 1.45 (m? 2H); 1.38 (s, 3H); 1.23 (s, 3H); 1.22 (m, 1H); 0.91 (d, J = 6.3 Hz, 6H); 0.81 (s? 3H). LC-MS 607.1, MH +. ESIPOS; AQA; Spray 4kV / Defoamer: 20V / Probe 250 C. Other compounds made basically according to the above experimental procedures are reported in Table D-5. Table D-5 Example number Structural chemical name and analysis data D.5.1 I Chemical property of palmitic HA: (2S) -4-[[Imine (acylamino) fluorenyl] amino] -2- [ (2-naphthylmethyl) -amino] -pentamidine, [(1 foot) -1-[(3 &amp;3,43,63; ^ 10-hexahydro-33,5,5-tri Fluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] Analytical data: MS: MH + 607.1; 1H-NMR (CDC13 + D20): 7.81 (m, 3H); 7.71 (s, br, 1H); 7.52-7.38 (m, 3H); 4.66 (s, br, 1H); 4.27 (dd, J = 8.8, 1.9 Hz, 1H ); 3.91 and 3.83 (ABq, 2H); 3.39-3.11 (m, 3H); 2.30 (m, 1H); 2.13 (m, 1H); 1.98-1.45 (m, 8H); 1.45 (m, 2H); 1.38 (s, 3H); 1.23 (s, 3H); 1.22 (m, 1H); 0.91 (d, J = 6.3 Hz, 6H); 0.81 (s, 3H) D.5.2 I Palmarity 〇- ~ 0 Chemical name: (2S) -4-[[Imine (acylamino) fluorenyl] amino] fluorenylfluorenyl) -amino] -pentamidine, N-[(lR) -H ( 3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3 -Fluorenylbutyl] Analytical data: MS: MH + 607.2 95014 -151-200529810

D.5.3 I palmarity, human r 0, 0, 0 Chemical name: (2S) -4-[[Imine (acylamino) methyl] amino] -2- [undecylamino] -Pentamidine, bucket [(1 foot) small [(3 &amp; 3,43,63,7) 10-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-Benzodioxofluoren-2-yl] -3-methylbutyl] Analytical data: MS: MH + 621.2 D.5.4 1 Synthetic chemical name: Η Π (2S) -4-[[ Imino (nitroamino) methyl] amino] -2-[(phenylmethyl Λ .0, yl) amino] -pentamidine, [[1 foot] small [(333,48, 63,7 &amp; 11) -Hexahydro S -3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxoborohydride \ χ Β ΪΗ -2-yl ] -3-Methylbutyl] π U Analytical dataMS: MH + 557.2 Example D.6 N-[(lS) -l-[[[(lR) -l _ [(3aS, 4S, 6S, 7aR)- Hexahydro_3a, 5,5_trimethyl_4,6_methylalkyl-1,3,2-benzodioxofluoren-2-yl] _3_methylbutyl] amino group] carbonyl group [[Imino (succinylamino) methyl] amino] butyl] -N41-fluorenyl) urea

(2S) -2-Amino-5-[[imino (nitroamino) methyl] amino] -pentamidine in Example C.1, [(111) 小 [(333,43 , 68,7311) -Hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl]-, hydrochloride (50 mg, 0.1 mmol) in CH3CN (4 ml), TEA (0.014 ml, 0.1 mmol) was added at room temperature with tritium Small isocyanate (0.014 ml, 0.10 mmol). The reaction mixture was stirred for 4 hours and then concentrated to dryness. The residue dissolved in DCM was washed with Η20; the organic layer was separated, and the solvent was removed under vacuum. Purification by flash chromatography on silica gel (DCM 95, MeOH 5) gave the title compound as a white powder (60 mg, yield 94 95014 -152- 200529810%). NMR (CDC13): 8.08 (s, br, 1Η); 7.98 (m, 1H); 7.79 (m, 2H); 7.57 (d, J = 8.2 Hz, 1H); 7.51-7_35 (m, 4H); 7.36 (d, J = 7.5 Hz , 1H); 7.17 (s, br, 1H); 6.67 (d, br, J = 6_6 Hz, 1H); 4.49 (m, 1H); 4.20 (dd, J = 8.5, L9 Hz, 1H ); 3.39 (m, 1H); 3.20 (m, 1H); 3_04 (m, 1H); 2_26 (m, 1H); 2.08 (m, 2H); 1.93 (t5 J = 5.6 Hz, 1H); 1.89- 1.55 (m, 7H); 1.39 (m, 1H); 1.32 (s, 3H); 1.31 (m, 1H); 1.21 (s? 3H); 1.20 (m5 1H); 0.85 (d, J = 6.0 Hz, 6H); 0.79 (s, 3H). LC-MS 636.3, MH + .ESIPOS; AQA; Spray 4kV / Defoamer: 20V / Probe 250 C. Other compound reports made basically according to the above experimental procedures In Table D-6. Table 0_6

Example No. Structure Chemical name and analytical data D.6.1

0_々0 Chemical properties of palmitate: 汴 [(18) -1-[[[(111) -1-[(3 &amp; 3,48,65,7 &amp; 1〇-hexaargon-3〇trimethyl -4,6 · Methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino Amino) methyl] amino] butyl] -N ·-(2-naphthyl) urea Analytical data: MS: MH + 636.4

D.6.2

Counteracting Chemical Name: N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-trisyl-4, 6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino ) Methyl] amino] butyl] -N · -phenylurea Analytical data: MS: MH + 586.3 D.6.3

Antagonistic chemical name: 汴 [(13) -1-[[((1 反) 小 [(3 旺 3,48,63,7 王 11) -hexaargon-3〇trisyl-4,6- Fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl [Amino] amino] butyl] -N'-heptylurea Analysis Data: MS: MH + 608.4 95014 -153- 200529810

D.6.4 D.6.5 D.6.6 D.6.7 D.6.8 D.6.9 95014

Confrontation

Confrontation

Confrontation

Counteracting chemical name: Dou [(13) 小 [[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 1〇-hexahydro-3 &amp;, 5,5-trimethyl- 4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino [Amino] amino] butyl] -N,-(l-: g: yl) urea Analytical data: MS: MH + 636.3; 1H-NMR (CDC13): 8.08 (s, br, 1H); 7.98 (m, 1H ); 7.79 (m, 2H); 7.57 (d, J = 8.2 Hz, 1H); 7.51-7.35 (m, 4H); 7.36 (d, J = 7.5 Hz, 1H); 7.17 (s, br, 1H) ; 6.67 (d, br, J = 6.6 Hz, 1H); 4.49 (m, 1H); 4.20 (dd, J = 8.5, 1.9 Hz, 1H); 3.39 (m, 1H); 3.20 (m, 1H); 3.04 (m, 1H); 2.26 (m, 1H); 2.08 (m, 2H); 1.93 (t, J = 5.6 Hz, 1H); 1.89-1.55 (m, 7H); 1.39 (m, 1H); 1.32 (s, 3H); 1.31 (m, 1H); 1.21 (s, 3H); 1.20 (m, 1H); 0.85 (d, J = 6.0 Hz, 6H); 0.79 (s, 3H) .___ Chemical name: Mu [(18) -1-[[[(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3〇trimethyl-4,6-fluorenyl-1 , 3,2-benzodioxobenzo-2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (nitroamino) fluorenyl] amino] butyl ] -Ν'- Eleven-base analysis data: MS: MH + 664.4 Name: 1 ^ [(13,211) -1-[[[(111) -1-[(3 &amp; 8,48,68,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4, 6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-hydroxypropyl] -N'-undecyl Urea analysis data: MS: [MH1 + 564.40_ Chemical name: Meaning [(13) 小 [[[(111) -1-[(3 玨 3,43,63,7 &amp; 11) -hexagon-3 &amp;, 5 , 5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -4- [ [Imino (nitroamino) fluorenyl] amino] butyl] -N '-[5- (ethoxyquinyl) pentyl] urea Analysis Data: MS: [MH] + 652.40_

Palmity

-154- Chemical name: Team [(13) -1-[[[(11〇-1-[(3 &amp; 3,48,63,7 &amp; 11) -hexahydro-3〇trimethyl-4,6 -Fluorenyl-1,3,2-benzodioxo-2-enyl] -3 -methylbutyl] amino] carbonyl] ice [[imino (nitroamino) fluorenyl ] Amine] butyl] -N '-(4-butylphenyl) urea Analytical data: MS: [M] H + 642.5_ Chemical name: 扑 [(13) -1-[[[(111) -1 -[(3 &amp; 3,43,63,7 冱 11) -Hexahydro-3,5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxoline Fluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] -N '-(4-heptane Analytical data of menses urine: MS: [Μ] Η + 700.7_ 200529810 Example Ό · 7 Once the radical is burned [(lRH _ [[(2S) -5 _ [[Imine (acylamino)) Methyl] amino] -2 _ [[(E) -3- (trien-2_yl) propan-2-enyl]] amino] small ketopentyl] amino3methylbutyl

In PS-HOBT (1-Methylbenzotriazole-6-sulfoamidomethyl polystyrene, 277 mg, 0.31 mmol, filling capacity 112 mmol / g) in DCM (6 ml ) And DMF (0.6 ml) in suspension, add 3_ 荇 丨 -acrylic acid (91.2 mg '0.46 mmol), DIC (diisopropylcarbodiimide, 022 ml' 1.40 millimoles) and DIPEA (0_05 ml, 0.19 millimoles). This suspension was shaken at room temperature for 3 hours, then the resin was filtered under nitrogen and washed with DMF (3x5 mL), DCM (3x5 mL), DMF (3x5 mL) and THF (3 X 5 mL) Times. Suspended the fully dried resin in DCM (6 liters) and DMF (0.6 ml), and added [(lR) -l-[[(2S) -2-amino-5- [ [Imino (nitroamino) methyl;] amino] small-pentylpentyl] amino] each methylbutyl] -dihydroxyborane hydrochloride (50 mg, 0.14 mmol Ear) and Dipea (0.06 ml, 0.20 mmol). The reaction mixture was shaken at room temperature overnight. The resin was filtered off, washed with DMF (10 mL) and DCM (2 mL), and the solvent was concentrated to dryness. The crude compound was purified by ISOLUTE SPE-SI normal phase cartridge (DCM, MeOH 1) to obtain the title compound (25 mg, yield 35%). NMR (DMSO + D2 0, 343K): 8.06 (s, 1H); 7.95 (d, J = 9.0 Hz, 1H); 7.94 (m, 95014 -155- 200529810 2H); 7.72 (d, 1H); 7.61 (d, J = 14.9 Hz, 1H); 7.55 (d, J = 9.0 Hz, 1H); 7.55 (m, 2H); 6.89 (d, J = 14.9 Hz, 1H); 4.40 (m, 1H ); 3.30-3.10 (m, 3H); 1.82 (m, 1H); 1.73-1.53 (m, 4H); 1.50-1.32 (m, 2H); 0.87 (d, J = 6.1 Hz, 3H); 0.86 ( d5 J = 6.1 Hz53H). LC-MS495.0, [M-18] H + .ESIPOS; AQA; spray 5kV / defoamer: 15V / probe 250 C. Others basically made according to the above experimental procedure Compounds are reported at

Table D-7. Table D-7 Example number Structural chemical name and analysis data D.7.1 Palmar f ^ jl η y Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (Nitroamino) methyl] amino] -2-[[((2E) -3- (2-methoxyphenyl) -1-onepropyl-2- / °. 'j: 0_ alkenyl] amino] _1_ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: MH + 475.0 D.7.2 Parapetical chemical name: Dihydroxyborane, [ (lR) -l-[[(2S) -5-[[Imine (nitroamino) 0 0H \ χ N ^^ NH o \ amido] amino] -2-[((Ε)- 2-methyl-3-phenylpropenylfluorenyl) amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18JH + 458.0 D.7.3 1 pair Palmitic H 8 f &quot; Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) jQT ^ YrVr methyl] amino]- 2-[(4- (4-fluorenylphenyl) butylfluorenyl) amino H-one 0, NH0 HL o are. Pentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 474.0 95014 156- 200529810

D.7.4 D.7.5

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((2RS) -2 -Phenylpropanyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 447.2 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(2- (4-isopropylphenoxy) ethenyl) amine Methyl] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 491.5 Chemical name: Dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imine (nitroamino) methyl] amino] · 2 [(5-keto-5-phenylpentamyl) amino] small ketopentyl] Amine] -3-methylbutyl] Analytical data: MS: [M-18] H + 489.5_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) methyl] amino] -2-[[(4RS) -H (l, l-dimethylethoxy) carbonyl] hexahydropyridine-4-carbonyl] amino]- 1-ketopentyl] amino] -3-methylbutyl] Analytical data:

D.7.8

MS: [M-18] H + 526.1 Chemical name: Dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2 -[(4-Diethylaminobenzyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data:

MS: [M48] H + 508.1_ Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2 -[((E) -2-Methylhex-2-enyl) amino H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 443.0 95014 -157- 200529810 D.7.10 ο, 〇Η \ χ Η &lt; Α Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine ) Methyl] amino] -2- [〇thiophen-3-carbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 425.6 D.7.11

〇-々0 Parapetal chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [(4-Isophenenyl) amino] micro-pentylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 461.3 D.7.12 0 0Η \ χ κ r palm chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[( 5-methylpyridine-2-carbonyl) amino] -1-Wylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 439.3 D.7.13 Pair Palm

OH Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (nitroamino) methyl] amino] -2-[(benzylidene ) Amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18] H + 419.4 D.7.14

For stupid chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((E ) -2-Butenefluorenyl) amino group> 1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data MS: [M-18JH + 383.2 D.7.15 I palmarity « Αν-H uu \ X, Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino]]-2 -[((E) -Penta-2,4-dienefluorenyl) amino] -1, ylpentyl] amino] -3-methylbutyl] Analysis Data: MS: [M-18JH + 395.4 95014 -158- 200529810 D.7.16 \ χμ r The chemical name of the palm: dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[imino (nitroamino) methyl]] Amine] -2-[(3,3-dimethyl-butylamyl) amino] -1-¾ylpentyl] amino &gt; 3-methylbutyl] Analytical data MS: [M-18] H + 413.0 D.7.17

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[5- (2,5-dimethylphenoxy) -2,2-dimethylpentanyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS : [M-18] H + 547.2 D.7.18 I pair palm 〇i oh 0 \ X o_ ~ o Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) methyl] amino] -2-[(2,2-Dimethylpentanyl) amino H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 427.5

D.7.19 Palmarity, x, Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[4Heptaphen-2-yl) butylfluorenyl] amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data MS: [M-18] H + 467.5

D.7.20 Palmar NΗ κ Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [ [5- (4-Fluorophenyl) pentamyl] amino] -1--ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 493.4 D. 7.21

〇V 0 \ χ, Para chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino]] 2-[(2,2-Dimethylhexyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data MS: [M-18] H + 441.0 95014- 159- 200529810 D.7.22

/ OH X Human NH Para palm chemical name: dihydroxyborane, [(1R) small [[(2S) -5-[[imino (nitroamino) methyl] amino] -2- [(Hex-2,4-alkenyl) amino] -1-ketopentyl] Amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 409.3 D.7.23

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[7 Sephen-2-yl) acrylfluorenyl] amino H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 451.4 D.7.24

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (nitroamino) methyl] amino] -2-[(5- Cyclohexylpentamyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 481.1 D.7.25 -AX, HOH \ x Palmitic chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[( (3R) -3,7-Difluorenyloct-6-enenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18 ] H + 467.3 D.7.26 ° WT 〇-% Palmitic chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine) methyl ] Amine] · 2-[[3-[(4-methylbenzyl) thio] propanyl] amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data : MS: [M-18JH + 507.0 D.7.27 0OvaNi i kH ^ \, x

NH Human OxO Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(4 -Pyrrole small phenylfluorenyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] MS: [M-18] H + 484.4 95014 -160- 200529810 D.7.28 FI Palmarity \ x N ^^ NH H Λ 0 x0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] Amine] -2-[(5-fluoro-2-oxophenylphenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [ M-18JH + 466.9 D.7.29 I Palmarity \ x o_ ~. Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5 · [[Imine (nitroamino) fluorenyl] amino] -2-[((2S) -2 -f-Butylfluorenyl) amino] small ketopentyl] amino] all methylbutyl] Analytical data MS: [M-18] H + 399.0 D.7.30 I palmarity \ χ K r Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(cyclopropanecarbonyl) amino]]- 1, ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 383.0 D.7.31 I palmarity 0 0H \ χ HA 0, 0 Chemical name: Dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] dong [[4-ethoxyphenylhydrazine) amino ] -1, ylpentyl] amino] -3_fluorenylbutyl] Analytical data: MS: [M-18] H + 463.5 D.7.32 I is awkward. 'N' ^ ΝΗ Η A Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2- [((E) -3- (4-Bromophenyl) prop-2-enyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 523.6 D.7.33 Palmar HL O '^^ O Chemical name: Dihydroxyborane, [(lR) -H [(2S) -5-[[Imine (nitroamino ) Fluorenyl] amino] -2-[[(2S) -2- (6-methoxynaphthalen-2-yl) -propanyl] amino] -1-ketopentyl] amino]- 3-Aminobutyl] Analytical data · MS: [M-18JH + 527.5

95014 -161-200529810 D.7.34. Price

NH A Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[1- ( 4-Methoxyphenyl) -cyclopropanecarbonyl] amino] -1-netylpentyl] amino] each methylbutyl] Analytical data: MS: [M-18] H + 489.4 D.7.35 0 \ x 〇Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(3-fluoro -4-methoxybenzylidene) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 466.9 D.7.36

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[[(Ε ) -3- (naphthalene-2-yl) prop-2-enylfluorenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data · MS: [M-18 ] H + 495.0; 1H-NMR: (DMS0 + D20, 343 K): 8.06 (s, 1H); 7.95 (d, J = 9.0 Hz, 1H); 7.94 (m, 2H); 7.72 (d, 1H) ; 7.61 (d, J = 14.9 Hz, 1H); 7.55 (d, J = 9.0 Hz, 1H); 7.55 (m, 2H); 6.89 (d, J = 14.9 Hz, 1H); 4.40 (m, 1H) ; 3.30-3.10 (m, 3H); 1.82 (m, 1H); 1.73-1.53 (m, 4H); 1.50-1.32 (m, 2H); 0.87 (d, J = 6.1 Hz, 3H); 0.86 (d , J = 6.1 Hz, 3H).

D.7.37

O 'Palm chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (nitroamino) methyl] amino] -2-[( 4-Fluoro-3-methylbenzyl) amino HW pentyl] amino] -3-fluorenylbutyl] Analytical data MS: [M-18] H + 451.3

D.7.38

I nt '\ ± \ χ〇Η Ν ^ ΝΗ Η L Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine) methyl ] Amino] -2-[[[[[((9H-g-9-yl) methoxybolyl] amino] butylammonyl] amino] small ketopentyl] amino] -3-methylbutyl ] Analytical data: MS: [M-18] H + 622.2 95014 -162- 200529810 D.7.39 \ χ H 〇Λ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5- [ [Imine (nitroamino) fluorenyl] amino] -2-[(4-benzylbenzyl) amino] small pentyl] amino] -3-fluorenylbutyl] analysis Data: MS: [M-18JH + 497.1 D.7.40 αΛ \ x

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (nitroamino) fluorenyl] amino] -2-[(3- Butenefluorenyl) amino] small "ylpentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18JH + 383.2 D.7.41

〇Comparative chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(ten Monomethyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 483.4 D.7.42 k Η (\ χ palladium NΗ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (nitroamino) methyl] amino] -2-[[4- (acetamidine Amine) Butylenyl] amino] -1-ketopentyl] amino] fluorenylbutyl] MS. [M-18] H + 442.2 D.7.43

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(6- Phenylhexyl) amino] micro-pentylpentyl] amino] -3-methylbutyl]-Analytical data: MS: [M-18] H + 489.27 D.7.44

I p-Benzene 丄 γ〇Η 〇I Η OH Λ〇 Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamine) methyl ] Amine] -2-[(5-phenylpentamyl) amino] -1-ketopentyl] Amino] -3-fluorenylbutyl]-Analytical data: MS: [M-18] H + 475.23 95014 -163- 200529810 D.7.45, ΑΝΛ 『α &quot; Η OH \ χ. ΝΗ • Λ Ο Chemical name: Dihydroxyborane, [(lR) -l-[[((2S) -5- [ [Imino (nitroamino) fluorenyl] amino] -2-[(3-methoxypropanyl) aminofluorenylpentyl] amino] -3-methylbutyl]- Analytical data: MS: [Μ · 18] Η + 401.16 D.7.46 \ .Χ. ΝΗ _ · Ν ^ Ο, 0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5 -[[Imine (nitroamino) methyl] amino] -2-[[2,2-Difluorenyl-3- (2-fluorenylpropenyl) -cyclopropanecarbonyl] amino]- 1-ketopentyl] amino] -3-methylbutyl]-Analytical data: MS: [M-18JH + 465.29 D.7.47

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(3- Methoxycyclohexylcarbonyl) amino H-ketopentyl] amino] -3-methylbutyl]-Analytical dataMS: [M-18JH + 455.57 D.7.48 I Palmarity

、 Fj! H 0 』々0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2 -[[3- (1Η-Indol-3-yl) -propionyl] amino H-ketopentyl] amino] -3-methylbutyl]-Analytical data: MS: [M-18 ] H + 486.24 D.7.49 Parapetical chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino]] 2-[((RS) -2-Cyclopent-2-enyl-ethenyl) amino] -1-Wylpentyl] amino] -3-methylbutyl] Analytical data · MS: [ M-18JH + 422.99 D.7.50

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (nitroamino) fluorenyl] amino] -2-[(5- Fluoren-2-yl-pentamyl) amino] small_ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 481.19 95014 -164- 200529810 D.7.51 pairs Palmness ° \ .Χ:

ΝΗ-n1 I Chemical name: Dihydroxyborane, [(1R) small [[(2S) -5-[[Iminino (nitroamino) methyl] amino] -2-[(6- 嗣-Heptyl) amino] -1-fluorenylpentyl] amino] -3-methylbutyl] Analytical data: MS: [Μ-18] H + 441.24 D.7.52

. \ X. Parapalm O 'Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2 -[(7-Keto-octyl) aminoaminostilbylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 455.47 D.7.53

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(hexane 醯Group) Amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18JH + 413.06

D.7.54

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(heptane (Amino) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data MS: [M-18] H + 427.14 D.7.55 ^ γ1 I Pair chemical name: Dihydroxyborane , [(LR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(3-octyloxy-propionyl) amino ] 小 -pentylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 499.17

D.7.56 Paraotropic 0_ &lt; N々0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino) ] -2-[(benzoxazole-6-carbonyl) amino] micro-pentylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 476.31 95014 -165 -200529810

D.7.57 | Palmer / OH 0, 0H, NH \ Λη Η 〇Λ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[ Methylamino) methyl] amino] -2-[(undec-2-enyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [ Μ-18] H + 481.41 D.7.58 1 pair of palm chemical names: ^ Η § dihydroxyborane, [(lR) -l-[[(2S) -5-[[imino (nitroamine ) Methyl] amino] -2-[(9-decenefluorenyl) amino] 4-ketopentyl] amine \ χ〇Η] -3-methylbutyl] Η U 〇_% analysis Data: MS: [M-18] H + 467.31 D.7.59 1 pair of palm chemical name: η ι dihydroxyborane, [(lR) -l-[[(2S) -5-[[imine group (nitrate Ylamino) γ-κB 0, r fluorenyl] amino] -2-[(tetradecanyl) amino] -1-_ylpentyl] amine χ β r 0 is. Methyl] -3-methylbutyl] Analytical data: MS: [M-18] H + 525.10

Other compounds prepared according to the procedures of Example D.7 above are reported in Table D-7A.

Table D-7A

Example number Structural chemical name and analytical data D.7.60 | Palm chemical name: κ ilnM Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino ) Methyl] amino] -2-[(11-fluorenylundecylfluorenyl) amino] small keto ° \ χ ° Ηamyl] amino] -3-methylbutyl] HL Eight analysis Data: MS: [M-181H + 508.5 D.7.61 1 pair of palm chemical name: η y dihydroxyborane, [(lR) -l-[[(2S) -5-[[imino (nitroamine Group) &gt; γΑΝ &gt; γ〇Η fluorenyl] amino] -2-[(9-cyano nano) amino HK pentyl] amine 0 ^ 〇〇Η \ χ 基] -3-fluorenyl Base] Ν ΝΗ Η 0Λ0 Analytical data: MS: [M-18] H + 480.1

Example D.8 Decylamine, H [[18,211) _1-[[[[(11〇-1-[(3Note 8,48,68,7 &amp; 11) -hexahydro_3 &amp;, 5,5-tri Methyl 95014 -166- 200529810 _4,6_methylalanyl_1,3,2_benzodioxofluorenyl group] -3-methylbutyl] amino group} tamino group-2-hydroxypropyl 】-

Dissolve capric acid (220 mg, 1.28 mmol, 1.2 equivalents) in anhydrous DMF (15 ml) at room temperature, add TBTU (410 mg, 1-28 mmol, 1.2 equivalents), and dissolve the formed The solution was stirred for 10 minutes. The mixture was brought to 0-5. After cooling at 0 ° C, NMM (0.35 ml, 3.2 mmol, 3 equivalents) was added, and then the (2S) -amino- (3R) -hydroxybutyric acid amidine of Example C.3 was added, and [(13)- 1 _ [[[(111) -1-[(3 &amp; 8,48,68,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] weiyl] hydrochloride (43 mg, 1067 mmol, 1 equivalent). The solution was stirred for 2 hours, then poured into water (200 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with the following solutions: 2% (20 ml) of citric acid, 2% (20 ml) of sodium bicarbonate, and 2% (25 ml) of sodium bicarbonate. The organic solution was dehydrated and dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to obtain 600 mg of oil, which was purified by silica gel chromatography (acetic acid acetate / n-hexane / 1/1) to obtain 540 houses. A white solid was suspended in ether (5 ml) and n-hexane (20 ml) overnight. This suspension was filtered to obtain 110 mg of a white solid. Yield: 20%. Analytical data: melting point 108-110 C, TLC stone gum (n-hexane / ethyl acetate g rf 0.33) · E · A · calculated value C (66.91%), Η (10.26%), N (5.38 %), B (2.08%); Found C (66.82%), Η (10.61%), N (5.35%), B (1.93%) 95014 167- 200529810 ^ -NMRCDMSO- ^): 8.81 (lH5br) ; 7.68 (1H5 d5 J = 8.80 Hz); 4.93 (1H, d, J = 5.2); 4.28 (1H, dd, J = 8.8, 4.3); 4.05 (1H, dd, J = 8.6, 1 · 8 ); 3.92 (1H, m); 2.52 (1H, m); 2.20 (1H, m), 2.17 (2H, t, J = 7.1); 2.00 (1H, m); 1.83 (lH, t , J = 5.8); 1.78 (lH, m); l_64 (lH, m); l_62 (lH, m); 1.49 (2H, m); 1.34 (lH, d, J = 10.0); 1.31-1.17 (21H , M); 1.04 (3H, d, J = 6.4); 0.91 · 0.83 (9H, m); 0_81 (3H, s). Other compounds prepared according to the above procedures include the following: Example D.8.1 (2S) -2 _ [(Benzyloxycarbonyl) amino] -4_methylpentanamine, N _ [(1S, 2R) _1-[[((1R) -1_ [(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2_benzodioxofluoren-2-ylb 3.methylbutyl] amino 1carbonyl] -2-hydroxy Propyl]-(Τ '1

SVy0, HO, Analytical data: TLC (CHC13 9 / MeOH 1, Rf 0.63), melting point 38-40 ° C, EA calculated value C (64.60%), Η (8.54%), N (6.85% ); Measured value C (62.44%), Η (8.24% Ν (7.47%). ^ NMRCDMSO- ^) 5η: 8.78 (lH, br); 7.82 (1Η5 d, J = 8.60 Hz); 7.52 (1Η , d, J = 8.1); 7.40-7.27 (6H, m); 5.02 (2H, br s); 5.00 (1H, d, J = 5.1); 4.28 (1H, dd, J = 8.6, J = 4.2) ; 4.12 (1H, q, J 7.8); 4.05 (1H, dd, J = 8.6, J = 1.8); 3_94 (lH, m); 2.52 (lH, m); 2.19 (lH, m); 2.01 (lH , M); 1.83 (lH, t, J = 5.8); 1.78 (lH, m); 1.74-1.55 (5H, m); 1.46 (2H, m); 1.32 (lH, d, J = 10.1); 1.24 (3H, s); 1.22 (3H, s); 1.04 (3H, d, J = 6.2); 0.91-0.82 (12H, m); 0.80 (3H, s) 95014 -168- 200529810 Example D.8.2 10 -(1,3-diketo_1,3_dihydro_iso &lt; indol-2-yl) _decylamine-] \ _ [(18), (211) -2-hydroxyl 1-[[ (1 拗 -1 _ [(3z, 48,68,7211) -Hexahydro-3 Note, 5,5_trimethyl_4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] -3-methylbutyl] aminocarbonyl] -propyl]-

Analytical data: TLC (CHC13 9 / MeOH 1, Rf ·· 83), E · A · Calculated value C (66.52%), Η (8.33%), N (6_37%); Found value C (66.76% ), Η (8 · 48 #%), Ν (6.31%). 1HNMR (DMSO-d6) 5η: 8.80 (lH, br); 7.85 (4Η, m), 7.67 (1Η, d, J = 8.80 Hz); 4.93 (1H, d, J = 5.5), 4.28 (1H, dd, J = 8.6, 4.0); 4.04 (1H, dd); 3.92 (lH, m); 3.56 (2H, t , J = 8.1); 2.49 (lH, m); 2.23-2.12 (3H, m); 2.00 (1H, m); 1.82 (lH, t, J = 6.6); 1.78 (lH, m); 1.73-1.53 (5H, m); 1.48 (2H, m); 1.33 (1H, d, J = 10.l); 1.31-1.17 (20H, m); 1_03 (3H, d, J = 6.2 ); 0.84 (6H, d5 J = 6.6); 0.80 (3H, s). Other compounds made according to the procedures of the above examples D.8, D.8.1 and D.8.2 are reported in Table D-8. in. Table D-8 Example number Structural chemical name D.8.3 4-Benzyl 4- (pyridin-3-yl) benzimidamine, N-[(lS? 2R &gt; l-[[[(lR) .l «[( 3aS, 4S5 6S, 7aR) _hexahydro_3a, 5,5-trimethyl-4,6-methylalkyl_1,3,2_benzodioxofluorenyl_2_yl] _3_methyl Butyl] amino] Jinyl] -2-Ethyl] 95014 -169- 200529810 D.8.4 1 Palmar (\: where 2-pyridoxamine, N-[(1S, 2R) -1 -[[[((1R) Small [〇3,43,63,7 &amp; foot) -Hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodi Oxyborin-2-yl] -3-methylbutyl] aminomethyl] -2-hydroxypropyl]. D.8.5 Para palmitate 丄 Β · 〇Α tridecylamine, hydrazine [( 13,211) small [[[(111) small [(338,43,68,7311) -hexahydro-3a, 5,5-dimethyl-4,6_methanyl-1,3,2-benzo Dioxobenzoyl-2-yl] -3-methylbutyl] amino-naked] _2_hydroxypropyl]. D.8.6 Para n ^^ γ Identifies 1αη ♦ 4-phenylbenzamide, 仏[(13,2 phantom-l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -A mouse-3a, 5,5-dimethyl-4,6_methanyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl]. D.8.7. Palmarity ---- -丄 Η · 〇β Η 6 \ ξAX 2,2- Dimethyldecylamine, hydrazone [(13,211) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trifluorenyl-4, 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -2-hydroxypropyl]. D.8.8 1 Properties σΛ: (4-phenoxy) benzamidine, N-[(lS, 2R) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2 -Hydroxypropyl]. D.8.9 1 Para palmitate, such as 5-butyl-2-pyridinecarboxamide, N-[(lS, 2R) -l-[[[(lR) -l- [ (3aS, 4S, 6S, 7aR) _Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 -Fluorenylbutyl] amino] carbonyl] -2-hydroxypropyl].

95014 -170- 200529810 D.8.10 j Paraben 4-propoxyl benzamidine, N-[(l S, 2R) · 1-[[[[(1 R) _ 1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] _2-Ethylpropyl]. D.8.11 3- (3-pyridyl) benzidine, N-[(lS, 2R) -l-[[[(lR) -l _ [( 3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxan-2-yl] -3 -Methylbutyl] amino] carbonyl] -2-hydroxypropyl]. D.8.12 6-phenyl-2-pyridinecarboxamide, N-[(lS, 2R) -1-[[[(lR ) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydradioxine- 2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-hydroxypropyl]. D.8.13 1 p-palm 3-propoxybenzamide, N-[(1 S, 2R ) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2 -Benzodioxin-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl]. D.8.14 I Para palmitate 1- &gt; Slow-brew amine, N-[(lS, 2R) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3 a, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] carbonyl]- 2-Hydroxypropyl]. D.8.15 1 Para palmitic 6-bromofluoren-2-carboxamidine, [[13,211] -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino group] carbonyl group] -2-Hydroxypropyl]. 95014 -171-200529810 D.8.16. Para-3-phenylphenylhydrazine, [[13,21〇-l _ [[[(lR) -l-[(3aS , 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-form Butyl] amino] carbonyl] -2-hydroxypropyl]. D.8.17 4- (2-Gaphenyl) benzidine, N-[(1S, 2R) -1-[[[(1R ) 小 [(3aS, 4S, 6S, 7aR) -hexaaza-3a, 5,5-dimethyl • 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl ] -3-Methylbutyl] amino] carbanyl] -2-viapropyl]. Intermediates used in Examples D.8.3, D.8.7, D.8.11, D.8.12, and D.8.13 Carboxylic acids are made according to literature procedures. Compound 2,2-diamidinodecanoic acid was prepared as described by Roth et al. In Met / CTzem 1992, 35, 1609-1617, and compound 4- (3-pyridyl) benzoic acid, 3 -(3-pyridyl) benzoic acid and 6-phenyl-2-pyridinecarboxylic acid were prepared according to the procedure described by Gong et al., In W 2000, (6), 829-831. Compound 3-propoxybenzoic acid was prepared according to the procedure described by Jones in J. C / iem. 5bc. 1943, 430-432. Example D.8.18 Reference 2_ Egen Carboxamide, meaning [(18) -1 _ [[[(111) _1 _ [(338,48,68,7 &amp; 11) -hexahydro_3 &amp;, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzobenzodioxo-2-yl] -3_methylbutyl] amino group]

Carbonyl] -2-aminomethylamidinoethyl] This compound has been obtained from (2S) -2-amino-3-aminomethylamidinopropylamidamine of Example C.3, [[11〇 小 [(3 &amp; 3,48,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzyl95014 -172- 200529810 Starting from 2-yl] -3-fluorenylbutyl] hydrochloride, it was basically prepared according to the procedures of Examples D.8, D.8.1 and D.8.2 above.

1H-NMR (DMSO-d6): 9.20 (1H, d, J = 1.29 Hz); 9.02 (1H5 d, J = 8.52 Hz); 8.91 (1H, d, J = 2.45 Hz); 8.81-8.76 ( 2H, m); 7.42 (1H, s); 6.95 (1H, s); 5.00-4.80 (1H, m); 4.30-4.08 (1H3 m); 2.85-2.72 (1H, m); 2.62-2.56 (2H , M); 2.25-2.15 (1H, m); 2.06-1 · 98 (1H, m); 1.84 (1H, t, J = 5.54 Hz); 1.8M.76 (1H5 m); 1.72-1.58 (2H5 m); 1.32-1.26 (1H? M); 1.23 (8H, d, J = 5.36 Hz); 0.85-0.79 (9H, m). Example D.8.19 Decamidine, N-[(1S)- 1-[[[((1R) 小 [(3 &amp; 8,48,68,7 &amp; 10-hexahydro-3 &amp;, 5,5_trimethyl-4,6_methylalkyl · 1,3,2 _Benzodioxofluoren-2-yl] -3-methylbutyl] amino Icarbonyl] _2_aminomethylethyl]

This compound has been obtained from (2S) -2-amino-3-aminomethylamidinopropanilamine of Example C.3, N _ [(1R) Small [(3 &amp; 3,43,63 &gt; 11) -hexahydro- 3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl &gt; 3-methylbutyl] hydrochloride started, basically The above is made according to the procedures of the above examples D.8, D.8.1 and D.8.2. Example D.8.20 'Butylbenzamide,] \ _ [(18) _1 _ [[[(111) -1 _ [(3 &amp; 8,48,68,7211) -hexagon-315,5-trimethylamine _4,6_methylalkyl_1,3,2_benzodioxoline_2_yl] -3-methylbutyl] amino] carbonyl] -2-aminomethylmethylethyl] 95014 -173- 200529810 palm

This compound has been obtained from (2S) -2-amino-3-aminomethylamidinopropionamine of Example C.3, [[1 幻 小 [(密, 48,68,73 幻 -hexahydro-3 \ 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] hydrochloride, basically based on The procedures of the above examples D.8, D.8.1 and D.8.2 are made.

Example D.9 Decylamine, N-[(lS) -l-[[[((lR) -l _ [(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl_4 , 6_methylalanyl_1,3,2_benzodioxolidine_2_yl] _3_methylbutyl] amino] Dynyl] -2-[(4-methylbenzylhydrazone Group) amino] ethyl] ·

Dissolve capric acid (330 gram '1.95 mol' 2 equivalents) in anhydrous dmF (20 ml) and add TBTU (620 mg, 1.95 mmol, 1.2) at room temperature under nitrogen equivalent). The solution was stirred for 10 minutes, cooled under the heart, and NMM (0.53 liters, 4.9 moles, 3 equivalents) and Example c.4 of (2S) -2_amino-3-[(4- 曱 Basic A Fluorenyl) amino] propylamine, small [(3as, 4S, 6S, 7aR)-', hydrogen-3a, 5,5-dimethyl-4,6_methanyl-i, 3,2- Benzodioxofluoren-2-yl] aspartylbutyl]-, hydrochloride (800 mg, us millimolar, 1 equivalent), and the resulting mixture was stirred at room temperature for 3 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (100 ml), and citric acid solution 95014-174-200529810 2% (50 ha), sodium bicarbonate 2% (50 ml), NaC12% ⑼ml). The organic solution was dried over anhydrous sodium sulfate, transitioned, evaporated, and suspended in ether (20 ml) over 30 minutes. This suspension was filtered and dried 'to give 330 mg of a white solid. Yield: 33%. Melting point: 1341-136. (:, 11 ^ Silicone (eluent n-hexane / ethyl acetate, Rf0.5) · EA calculated value C (69.33%), Η (9.37%), N (6.74%), B (1.73%); measured Values C (%), Η (%), Ν (23%), B (%) ·

1HNMR (DMSO-d6) 8.74 (lH, d, J = 3.5 Hz); 8.25 (1¾ t, J = 5.6); 7.95 (1Η, d, J = 7.9); 7.71 (2H, d, J = 8.1 ); 7.25 (2H, t, J = 8.1); 4.59 (lH, m); 4.1 · (1Η, dd, J = 1.8, 8.8); 3.49 (2H, m); 2.59 (lH, m); 2.35 (3H, s); 2.20 (lH, m); 2.09 (1H, t, J = 7.3); 2.02 (lH, m); l_83 (lH, t, J = 5.5); 1.78 (1¾ m); 1 · 62 (2H, m); 1.44 (2H, m); 1.36-1.21 (17H, m); 1.25 (3H, s); 1.22 (3H, s); 0.85 (3H, t, J = 6.8); 0.80 ( 9H, m). Example D.10

2-S-decylaminoamino-3- (hexamidineamino) · propanamidin ,,-[(18) -1-[[(111) 小 [(3aS, 4S, 6S, 7aR) -six Argon-3a, 5,5-trimethyl-4,6-methylalkyl_1,3,2_benzodioxofluoren-2-ylb 3-methylbutyl] amino group] carbonyl group]

Dissolve mg capric acid, 0.98 mmol, 1.2 equivalents) in anhydrous DMF (15 mL), and add TBTU (310 mg, 0.98 mmol, 1.2 equivalents) at room temperature under nitrogen. The solution was stirred for 20 minutes, cooled at 0-5 ° C, and 95014 -175-200529810

Add NMM (.271 ml, 2.46 mmol, 2.5 equivalents) and each amine group of Example 0.5_3- (hexamidineamino) -propanilamine, Ke ⑽ + post office Slightly called hexahydro-3a, 5,5-dimethyl_4,6_methylalkyl-i, 3,2-benzodioxofluorenyl] _3_methylbutyl] amino] Group], hydrochloride (400 mg, 0 g 2 mmol, 1 equivalent), and the resulting mixture was stirred at room temperature for 3 hours. The solution was poured into water (150 ml), extracted with ethyl acetate (100 ml), and washed with 2% (50 ml) of citric acid solution, 2% (50 ml) of sodium bicarbonate, and 2% (50 ml) of NaCl. . The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated, and suspended in ethyl acetate (20 ml) for 30 minutes. The suspension was filtered and dried to obtain 230 mg of a white solid. Yield 47%. Analytical data: melting point 135-137 ° C, TLC silicone (eluent hexane / ethyl acetate 2/1, R.f &gt; 0.27) · Ε · Α · calculated value C (67.64%), Η (10.35%), N (6.96%); found C (66.93%), Η (10.29%), N (7.14%), ^ NMRCDMSO-dg) (5η: 8.67 (1H5 d, J = 2.9 Hz); 7.83 (1H5 d5 J = 8.2); 7.67 (1H, t, J = 5.5); 4.41 (1H, m); 4.10 (1H, dd, J = 1.5, 8_6); 3.25 (2H, m); 2.56 (1H, m); 2.20 (lH, m); 2.13-1.95 (5H, m); 1.84 (lH, t, J = 5.5); 1.78 (lH, m); 1.64 (2H, m ); 1.46 (4H, m); 1.35-1.15 (27H, m); 0_84 (9H, m); 0.79 (3H, s). Example D.ll 2-S · decanoylamino-3- (4 -Fluorosulfonylamino) propylammonium, 1 ^ [(18) -1-[[(111) · l-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5- Trimethyl-4,6_methylalkyl-1,3,2_benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] 95014 -176- 200529810

Decanoic acid (160 mg, 0.94 mmol, 1.2 eq) was dissolved in anhydrous DMF (20 ml) and TBTU (300 mg, 0.94 mmol, 1.2 eq) was added at room temperature under nitrogen. The solution was stirred for 20 minutes, cooled at 0-5 ° C, and NMM (0.259 ml, 2.36 mmol, 2.5 equivalents) and 2-S-amino-3- (4-fluoro group of Example C.6 were added Sulfonylamino) Propanamide, N-[(lS) _1-[[(lR &gt; l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4 , 6 · Methyl-1,3,2-benzodioxol-2-yl] -3-methylbutyl] aminomethyl], hydrochloride (430 mg, 0.78 mmol , 1 equivalent), and the resulting mixture was stirred at room temperature for 2 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (100 ml), and washed with the following solution: citric acid 2% (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, transitioned, evaporated, and purified by silica gel chromatography (eluent n-hexane / Ethyl acetate 2/1). The solvent was evaporated and n-hexane was added to obtain 100 mg of a solid. Yield 19%. Analytical data. Melting point 83-85 ° C, TLC silicone (eluent hexane / Ethyl acetate 2 / 15R.f. = 0.53) .1H NMR (DMSO-d6) (5H: 8.45 (1H, d, J = 3.8 Hz); 7.83 (3H, m); 7.63 (1H t, J = 6.2); 7.42 (2H, t, J = 8.8); 4.40 (lH, m); 4.12 (lH, dd, J = 1.5, 8.6); 2.95 (2H, m); 2.64 (lH, m ); 2.21 (lH, m); 2.17 (2H, t, J = 7.3); 2.01 (lH, m); 1.83 (lH, t, J = 5.5); 1.78 (lH, m); 1.62 (2H, m ); 1.45 (2H, m); 1.4-1.1 (23H, m); 0.87-0.8 (9H, m); 0.79 (3H, s) 95014 -177- 200529810 Example D.12 2-S-decanol Amino_3_ (3,4 · dimethoxyphenylacetamido) propanamide, Wen 18) -1-[[(111) -1-[(3 略 48,68,70%)- Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluorene_2_ylbu 3-methylbutyl] amino] several groups ]

Decanoic acid (80 mg, 0.48 mmol, 1.2 equivalents) was dissolved in anhydrous DMF (20 mL), and TBTU (150 mg, 0.48 mmol, 1.2 equivalents) was added at room temperature under nitrogen. The solution was stirred for 20 minutes, cooled at 0-5 ° C, and NMM (0.13 ml, 1.2 mmol, 2.5 equivalents) and 2-S-amino-3- (3,4- Dimethoxyphenylacetamido) propanamide, N _ [(1S) small [[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl], hydrochloride (230 mg, 0.4 mmol) Ear, 1 equivalent), and the resulting mixture was stirred at room temperature for 2 hours. The solution was poured into water (200 ml), extracted with ethyl acetate (100 ml), and washed with the following solutions: citric acid 2% (50 ml), sodium bicarbonate 2% (50 ml), NaCl 2% (50 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated, and purified by silica gel chromatography (eluent n-hexane / ethyl acetate 1/1). The solvent was evaporated to give 100 mg of a glassy solid. The yield was 35.7%. Analytical data ·· TLC silicone (eluent hexane / ethyl acetate 1/1, R.f &gt; 0.53). Ε · Α · Calculated value C (67.13%), Η (9.25%), N (6.02% ); Measured value C (65.38 95014 -178- 200529810% X Η (9.20%)? N (5.49). 1Η NMR (DMSO-d6) (5Η: 8.65 (1Η, d, J = 3.5 Hz); 7 · 84 (2Η, m); 6.83 (2Η, m); 6.72 (1Η, dd, J = 1.7, 8 · 1); 4.43 (1Η, m); 4 · 10 (1Η, dd, J = 1.8 , 8.6); 3.72 (3H, s); 3.70 (3H, s); 3.30 (2H, s); 3.27 (2H, m); 2.58 (1H, m); 2.19 (lH, m ); 2.02 (3H, m); 1.84 (lH, t, J = 5.5); 1.78 (lH, m); 1.63 (2H, m); 1.43 (2H5 m); 1.35-1.15 (23H, m) ; 0.87-0.8 (9H, m); 0.79 (3H5 s). Example D.13

2-S-decylaminoamino-3- (phenylureido) propanilamine, N-[(lS) -1-[[(lR) -l-[(3aS, 4S, 6S, 7aR) _six Argon-3a, 5,5-trimethyl-4,6-methylalkyl 4,3,2-benzodioxofluoren-2-yl] _3_methylbutyl] amino] carbonyl]

ΗΝ 〇ό Dissolve capric acid (170 mg, 0.99 mmol, 1.2 eq) in anhydrous DMF (20 ml), and add TBTU (310 mg, 0.99 mmol, 1.2 eq) at room temperature under nitrogen. . The solution was stirred for 20 minutes, cooled at 0-5 ° C, and NMM (0.27 ml, 2.4 mmol, 2.5 equivalents) and 2-S-amino groups (phenylureido) of Example C.8 were added. Propylamine, &gt; ^ [(18) -1-[[(111) -1 _ [(3 &amp; 8,48,68,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4 , 6-Methylalkyl-l, 3,2-benzodioxofluoren-2-yl] _3_fluorenylbutyl] amino] carbonyl], hydrochloride (420 mg, 0.82 mmol, i Equivalent), and the resulting mixture was stirred at 0 t for 2 hours. The solution was poured into water (200 liters), extracted with ethyl acetate (100 ml), and washed with the following solution: # IS 夂 2% (50 ^: liters), sodium bicarbonate 2% (50 Ml), NaCl 2% (50 95014 -179- 200529810 ml). The organic solution was dried over anhydrous sodium sulfate, filtered, evaporated, and suspended in diethyl ether (20 ml). After 1 hour, filtered, and dried under vacuum to obtain 140 mg of a white solid, which was purified by silica gel chromatography. (N-hexane / ethyl acetate 1/1). Yield 25%.

Analytical data: TLC silica gel (eluent hexane / ethyl acetate 1 / 丨, R f = 〇4y ^ NMRCDMSO- ^) · 8.73 (lH5d? J = 3.1Hz); 8.64 (1H, br s); 7.97 (lH , D, J = 8.2); 7.36 (2H, d, J = 8.1); 7.19 (2H, t, J = 8.1); 6.87 (lH, t, J = 8.1); 6.1 (lH, t, J = 6_0 ); 4.44 (lH, m); 4.10 (lH, dd, J = 1.8, 8.6); 3.41 (lH, m); 3.22 (lH, m); 2.59 (lH, m); 2.19 (lH, m); 2.10 (2H, t, J = 7.3); 2.02 (1H, m); 1.84 (lH, t, J = 5.5); 1.78 (lH, m); 1.64 (2H, m); 1.46 (2H, m); 1.35-1.15 (23H, m); 0.87-0.8 (9H, m); 0.79 (3H, s) · Example IK14 2-aminoacetamidamine, bucket [(18) 小 [丨 [(111) -1- [(3 &amp; 8,48,68,7 &amp; 11) _Hexahydro-3 &amp;, 5,5_trimethyl-4,6-methylalkyl-1,3,2_benzodioxoline- 2-Methyl 3-methylbutyl] amino] carbonyl] -4-[[imine (acylamino) methyl] amino] butyl], hydrochloride

To a solution of N-Boc-glycine (383 mg, 2.18 mmol) in anhydrous dichloromethane (20 ml), add N-methylmorpholine (275 μl, 2.5 mmol) . The mixture was allowed to cool to -15 ° C and then isobutyl pivalate (286 μl, 1.2 mmol) was slowly added. After 15 minutes, add (2S) -2-amino-5-[[imine (nitroamino) fluorenyl] amino] pentamidine N-[(1R) small [(3aS, 4S, 6S, 95014 -180-200529810 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxoline_2_yl]- 3-methylbutyl] -hydrochloride (1. 00 g, 20 mmol) with additional methylmorpholine (275 μl, 2.5 mmol). The reaction mixture was stirred at _15 ° c_1 ° C for 4 hours and then concentrated to a small volume, and the solution was separated between ethyl acetate (1 ml) and water (50 liters). Water The phases were further extracted with ethyl acetate (20 ml). The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in ethyl acetate (5 ml) and the solution was added dropwise to hexane ( 120 ml) while stirring at room temperature. The solid was collected by decantation and dried under vacuum (1.18 g, 95%). A portion of this boc-protected intermediate (1.08 g, 1.73 mmol) was made. Mol) was dissolved in THF (15 ml), and then a 4N solution of HC1 in dioxolane was added. After stirring at room temperature for 5 hours, the mixture was concentrated 'and the residue was triturated with ethyl scale (50 ml). The white solid formed was collected by filtration, washed with ethyl acetate, and dried under vacuum to yield 856 mg of the title compound (88% yield). ^ NMRCDMSO ^): 8.76 (lH, d5J = 3.1 Hz); 8.68 (1H, d5 J = 8.1); 8.56 (1H, br); 8.06 (3H, m); 7.91 (2H, br); 4.43 (1H, m); 4.14 (1H , Dd, J = 8.6, J = 1.6); 3_60 (2H, m); 3.15 (2H, br); 2.67 (1H, m); 2.23 (1H, m); 2.04 (lH, m); 1.87 (lH, t, J = 5.8); 1.81 (lH, m); 1.75-L60 (3H, m); 1.52 (3H, m); 1.41-1.28 (3H, m); 1.27 (3H, s) ; 1.23 (3H, s); 0.86 (3H, d, J = 6.4); 0.84 (3H, d, J = 6.4); 0.81 (3H? S). Example D.15 3-aminopropylamidamine, N -[(1S) -1 _ [[[(1R) Small [e.g. 8,48,68,7 &amp; 11) -hexahydro-3 &amp; 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl 1-4-[[imino (acylamino) methyl] amino] butyl Group]; hydrochloride 95014 -181-200529810

In Example D.3.118, 3-[[(1,1 · Dimethylethoxy) carbonyl] amino] propanilamine [(13) 小 [[[((111) -1-[(3 &amp; 3 , 43,63,7311) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl] _3_form Butyl] amino] kisyl] -4-[[imino (sucralylamino) methyl-] amino] butyl]-(42 mg, 0.075 mmol) in ether (1.0 ml) To the solution cooled at 0 ° C, a 10% v / v solution of hydrogenated hydrogen in ether (2 ml) was added. The mixture was stirred for 5 hours while warming to room temperature. The solid formed was collected by filtration, washed with diethyl ether (3 x 3 mL), and dried under vacuum to give 33 mg of the title compound (76% yield). LC-MS 538.7, MH + .ESIPOS; AQA; spray 4kV / demister: 20V / probe 250 C ·

Other compounds prepared from the corresponding Boc-protected compounds in Table D.3 according to the examples above are reported in Table D-15 below. Table D-15 Example number Structural chemical name and analysis data D.15.1 | Counter chemical name: CH Η Π (4RS) -hexahydropyridine-4-carboxamide, N-[(lS) -l-[[ [(lR) -l-[(3aS, 4S, 6S, 7aR) -A 0 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo 1 χ di Oxoborohydrin-2-yl] -3-fluorenylbutyl] amino] carbonylfluorenyl U group] -4-[[iminofluorenylamino) methyl] amino] butyl 0 ν0 group], HC1 salt analysis data: MS: MH + 578.1 95014 -182- 200529810 D.15.2-. SfiT * \ χ, Ν ^^ ΝΗ 〇 〇Λ Chemical name: (RS) -hexahydropyridine-2-carboxamide, N -[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2 -Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl]; HC1 salt analysis data: MS: [MH] + 578.2 D.15.3-Palmar π ο '^^ ο Chemical name: (2S) -hexahydropyridine-2-carboxamide, N-[(lS) -l -[[[(lR) -H (3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2 · benzodioxoline Orn-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[ Imine (nitroamino) fluorenyl] amino] butyl]; HC1 salt analysis data: MS: ΓΜΗ1 + 578.2 D.15.4 1 掌 palmity CH S human r 〇 is 〇 Chemical name: (2R)-six Argonpyridine-2-carboxamidine, N-[(lS) -l-[[[((lR) -1-[(3aS, 4S, 6S, 7aR)-^ argon-3a, 5,5-trifluorenyl -4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino Amino) methyl] amino] butyl]; HC1 salt analysis data: MS: ΓΜΗ1 + 578.8 Example D.16 Synthesis of other compounds

Following the procedures of Examples D.9-D · 13, the following compounds can be prepared by reacting decanoic acid with the intermediate of Example C.9. D.16.1 Decylamine, N-[(lS) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6 -Methylalkyl-I, 3,2-benzodioxofluorenyl] -3-fluorenylbutyl] amino] carbonyl] -2- (ethylamido) ethyl] -r-Qin D. 16.2 1 Decylamine, N-[(lS) -H [[(lR) Small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl · 1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino group] carbonyl] -2- (9 · thenylfluorenyloxyamine 'VJ ^ Γ ° Formamyl) ethyl]-95014

-183- 200529810

D.16.3 Decylamine, N-[(1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2- (pentyl-ureido) ethyl]-Q ,. . D.16.4 Decamidine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl- 4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2- (methanesulfonamido) ethyl Radical]-o = s = o 1 D.16.5 Decylamine, N-[(1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-[(ethyl Oxycarbonyl-succinyl) -amidamine] ethyl]-—f 0 D.16.6 4 · Butylbenzidine N-[(lS) Small [[[((lR) -l-[(3aS, 4S , 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl] amino] carbonyl] -2-[(fluorenylcarbonylamido) ethyl]-[H NMR (DMSO-d6): 9.79 (1H, d); 8.32 (1H, d); 7.8 (2H, d); 7.3 (8H, m); 5.05 (2H, q) 4.7 (1H, q); 4.1 (1H, d); 3.45 (2H, m); 2.6 (3H, m); 2.2 (1H, m) ; 2.0 (1H, m); 1.85 (2H, m); 1.65 (4H, m); 1.3 (5H, m); 1.25 (6H, d) 0.9 (3H, t); 0.80 (9H, m). 95 ° -100oC · D.16.7 4-Butylbenzamide, N-[(lS) Small [[[((lR) -l-[(3aS, aS, 6S, 7aR)- Hydrogen-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl + 3-fluorenylbutyl] amino] carbonyl] -2- (1H-pyrazine) ethyl] -D.16.8 Decylamine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl]- 2-[(Methoxycarbonylamido) ethyl] -lH NMR (DMSO-d6): 8.69 (1H, d); 7.85 (1H, d); 7.35 (5H, m); 7.05 (1H, t); 5.05 (2H, m) 4.45 (1H, q); 4.1 (1H, d); 3.3 (2H, m); 2.65 (1H, m); 2.2 (1H, m); 2.1 (3H, m); 1.85 ( 2H, m); 1.65 (2H, m); 1.45 (2H, m); 1.25 (22H, m); 0.8 (12H, m) I pair of palms 95014 184- 200529810

4-phenoxy benzamidine, N-[(1S) -1-[[[((1R) -1 [(3 玨 8,48,68,7 &amp; 11) -hexaaza-3 &amp;, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(¥ Oxycarbonylamido) ethyl] -lR NMR (DMSO-d6): 9.8 (1H, d); 8.4 (1H, d); 7.9 (2H, d); 7.4 (2H, t); 7.3 (6H, m ); 7.25 (2H, m); 7.05 (4H, m); 5.05 (2H, q) 4.7 (1H, q); 4.05 (1H, d); 3.45 (2H, m); 2.65 (1H, m); 2.2 (1H, m); 2.0 (1H, m); 1.80 (2H, m); 1.65 (2H, m); 1.3 (4H, m); 1.25 (6H, d) 0.8 (9H, m). Melting point 100 ° -103oC.

Example D.17

4-Butylbenzidine, N _ [(lS) _H [[(lR) -l _ [(3aS, 4S, 6S, 7aR) -hexahydro_3a, 5,5 · trimethyl-4,6_ Methylalkyl_1,3,2_benzodioxoline_2 · yl] _3_methylbutyl] amino] carbonyl-2- (aminoethyl) -hydrochloride

0 VklLJ

Make 4-butyl benzamidine of Example D.16.6, N _ [(lS) _H [[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] kisyl] -2-[(benzyloxycarbonyl Amido) ethyl]-(400 mg, 0.62 mmol, 1 eq) was dissolved in 1,4-dioxolane (10 ml) and methanol (5 ml). To this solution, Pd / C 10% (40 mg) and 4 N HC1 1,4-dioxolane (1.1 equivalents) were added. The mixture was hydrogenated at 1 bar. When the reaction was completed, Pd / C was filtered on diatomaceous earth, and the solvent was removed under reduced pressure to obtain a white foam. Yield: 95%, 320 mg. Analytical data: ^ NMRCDMSO ^): 8.76 (lH5d); 8.55 (1H5 d); 8.15 (3H? Br s); 7.95 (2H, d); 7.25 (2H, d); 4 · 8 (1H, m ); 4.2 (1H, d); 2.80 (1H, m); 2.62 (2H, t); 2.23 (lH, m); 2.04 (lH, m); 1.87 (lH, t); 1.80 ( lH, m); 1.75-1.50 (2H, m), 95014 -185- 200529810 (2H, m); 1.4M.20 (6H, d), (6H, m); 1.0-0.80 (3H, d); (3H, d); (3H, s), (3H, t). Example D.18 2-S_ (4-Butylbenzylamino) · 3- (2-pyridinecarbonylamino) -sense [ (18) -1-[[(111) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzene Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl]

Dissolve 2-pyridinecarboxylic acid (76 mg, 0.61 mmol, 1.1 equivalents) in anhydrous DMF (5 ml) and add TBTU (200 mg, 0.61 mmol, 1.1 equivalents) at room temperature under nitrogen . The solution was stirred for 15 minutes, cooled at 0-5 ° C, and NMM (0.20 ml, 1.85 mmol, 3.3 eq.) And 4-butylbenzamide, N _ [( 1S) Small [[[((iR) 小 [(3 略 43,68,7 design) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo Dioxo-2-yl] -3-methylbutyl] aminomethyl] -2- (aminoethyl) -hydrochloride (310 mg, 0.56 mol '1 equivalent), And the resulting mixture was stirred at 25 ° C for 4 hours. The solution was poured into water (100 ml), extracted with ethyl acetate (50 ml), and washed with the following solutions: citric acid 2% (50 ml), NaCl 2% (50 ml), sodium bicarbonate 2 % (50 ml), NaC 12% (50 ml). The organic solution was evaporated with anhydrous stone '1L &amp; L sodium dehydrated and dried', and suspended in acetonitrile + hexane for 1 hour to obtain a white solid, which was filtered and dried under vacuum to obtain White powder. 95014 • 186- 200529810 Yield 52% · 180 mg · Analytical data: melting point 70-72 ° (: ^ NMRCDMSO ^): 9.20 (1H5s); 9.0 (lH, t); 8.85 (lH5d); 8.8 (1H3 d ); 8.78 (lH, d); 8.60 (lH, d); 7.82 (2H, d); 7.35 (2H, d); 4.8 (lH, m); 4.1 (lH, d); 3.80 (lH, m) ; 3.62 (lH, m); 2.82 (lH, b); 2.65 (2H, m); 2.2-2.0 (2H, m); 1.80 (1H, m); 1.75-1.50 (2H, m), (2H, m); 1.41-1.20 (6H, d), (6H, m); 1.0-0-0 · 80 (3H, d); (3H, d); (3H, s), (3H, t).

Example D.19 4-Butylbenzamide,] \-[(18) Small [[[(111) Small [e.g. 8,48,68,731〇-hexahydro-32,5,5-trimethyl-4 , 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl group] -3 · methylbutyl Iamino group] carbonyl group] -2- [4-fluoro-benzenesulfonylamine] Ethyl] ·

Make 4-butylbenzamide of Example D-17, N-[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Fluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluorenyl-2.yl] -3-methylbutyl] amino] carbonyl] -2-[(benzyloxycarbonylfluorene Amine) Ethyl K2 75 g, 5.02 mmoles, 1 equivalent), dissolved in anhydrous dioxane at 0-5 ° C. To this solution was added gasified 4-fluorobenzite scutellaria (ΐ.07g, 5.52 millimoles' U equivalent), and after a few minutes, N-fluorenylmorphine, Lin ( NM) (1.11 g, 11.04 millimoles, 2.2 equivalents). Mix the mixture at 0-5. Searching and stirring for 30 minutes' followed by 1 hour at 10 ° C. The solvent was removed under reduced pressure, the crude product was dissolved in ethyl acetate, and 2% (50 ml) of citric acid solution, followed by carbon 95014-187-200529810 2% sodium hydrogen acid solution (50 ml) and chlorine Wash with sodium 2% solution (50 ml). The solution was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The crude material was purified by silica gel chromatography (eluent ethyl acetate / n-hexane 1/2). The collected fractions had been evaporated under reduced pressure, and the white solid was suspended in ether, filtered, and vacuumed. And dried to obtain white wax. Yield: 60%, 2 g. Analytical data: 1H NMR (DMSO-d6): 8.60 (1H? D); 8.30 (ltt? D); 7.85 (3H, m); 7.8 (2H, φ d); 7.38 (2H3 d); 7.30 (2H5 d) ); 4.62 (1H? M); 4.15 (1H5 d); 3.25 (2H? Br); 2.61 (3H, m); 2.3-2.0 (lH, m); (lH, m); 1.80 (lH, m) 1 · 75-1 · 50 (2Η, ηι), (2H, m); 1 · 41-1 · 20 (6H, d), (6H, m); 1 · 0_0 · 80 (3H, d); (3H, d); (3H, s), (3H, t). Example D.20 4-Butylbenzidine,] \-丨 (18) _1 _ [[((1 拗 小 [Coffee8 # 8,68,7 &amp; hexaargon-33,5,5 · trimethyl-4,6_methanyl_1,3,2_benzodioxolidine-2_yl _] _ 3 · form Butyl] amino] carbonyl] -2-[(2,5-dimethyl-2Η-pyrazole) carbonylamino] ethyl

Let D-17 benzylamine, N-[(lSH-[[[((1R &gt; 1 _ [(3aS, 4S, 6S, 7aR) _hexahydro-3 \ 5,5-dimethyl -4,6-methylalanyl-1,3,2-benzodioxolane_2_yl] -3-fluorenylbutyl] aminomethyl] _2 _ [(benzyloxycarbonylamidino) ethyl [] 9 (0.9 g, 1.64 mmol, 1 eq.) Was dissolved in anhydrous dichloromethane (10 ml). The resulting solution was cooled to 0 ° &lt; T &lt; 5 ° C, and Ν was added -Methyl-morpholin (0.38 g, 95014-188-200529810 3 is mole, 2.3 equivalents). To the mixture, gasification was added to the dimethyl industry 碳 -5-carbon brewer 5458_67_8]) ( 0.286 mg, [8 millimoles, equivalent ". The mixture was allowed to stir for 1 hour 'and then the temperature was raised to the wrist. The kun compound was decompressed: evaporated and suspended in ethyl acetate (50 ml). , Washed with a bar-like acid solution (30 liters), 2% sodium bicarbonate (30 ml), 2% sodium gaseous (30 ml). The organic layer was dried over anhydrous sodium sulfate, and decompressed under reduced pressure. The crude product was purified by silica gel chromatography (eluent ethyl acetate / n-hexane φ 8/2). The collected fractions were evaporated, A white powder was obtained, suspended in diethyl ether, and filtered to obtain the desired compound. Yield 65%, 65 mg. Rf. 0.62. Analytical data: melting point 62-64 ° C. ^ NMRCDMSO ^): 8.82 ( lH5d); 8.40 (2H, m); 7.85 (2H5 d); 7.3 (2¾ d); 6.5 (lH, s); 4.8 (lH, m); 4.15 (lH, d); 3.9 (3H, s); 3.61 (2H, m); 2.65 (3H, m); 2_25 (lH, m); 2.15 (3H, s); 2.0 (lH, m); 1.80 (lH, m); 1.75-1.50 (4H, m) 1.4M.20 (5H5 m) 5 (6H, m); 0.90 (3H, t); 0.8 (9H, m); • Example D.21 4-Butylbenzidine, N- 丨 (18) _1 _ [[[(1 拗 _1-[(3 &amp; 8,28,68,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2- (4-methylphenylureidosulfonylamino) ethyl]-

95014 -189- 200529810 Example D · 17 of 4-Butylbenzidine, which SH-[[[[(1RH-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4, dialkyldioxobenzodioxo-2-oxo] 2-methyl] 3methylbutyl] yl] kisyl] · 2 [[(Tetraoxoylamine) ethyl] _ (〇 · 7 grams, 1.27 millimoles, 1 equivalent) were dissolved in anhydrous THF (10 mL), and the solution was cooled at 0-5 C. Triethylamine (0.4 mL, 18 millimoles, 2 2) was added (Equivalent) and (4-methylphenyl) _ureido_continuine (0.34 g, 138 mmol, 1.09 equivalent) with Example G.1X. This suspension was stirred at 25 t for 1 hour. And then poured into citric acid solution (30 ml) and extracted with ethyl acetate (50 ml). The organic solution was washed with a 2% solution of gasified sodium, dehydrated and dried over anhydrous sodium sulfate, The crude product was obtained by evaporation under reduced pressure, and the crude product was purified by silica gel chromatography (&gt; Ethyl acetate / ethyl acetate / n-hexane burned l / l) Rf 0.64. The collected fractions have been collected. It was evaporated and the oil was co-evaporated with ether to give a white foam. Yield 31%, 280 mg. Analytical data: melting 115-120 ° C. ^ NMRCDMSO ^): 8.80 (lH, s); 8.40 (1H, d); 7.82 (2H, d); 7.3 (2¾ φ d); 7.25 (2H, d); 7.00 (2H, d); 4.62 (1H, m); 4.15 (1H, d); 2.61 (3H, m); 2.3-2.0 (3H? s); 1.80 (lH5m); 1.75 (2H3 m) 5 1.6 (4H, m)? 1.2 (13H, m); 0.9 (3H, s), 0.8 (9H, m) Example D.22 4-phenoxybenzamide, Qin [(18) _1 _ [[[(111) _1- [(3 &amp; 8,48,68,7 &amp; 11) _Hexahydro-3a, 5,5_trimethyl-4,6-methylalkyl_1,3,2_benzodioxoline_2 _Yl] -3_methylbutyl] amino] carbonyl] -2- (3-phenyl-ureido) ethyl]-95014 -190- 200529810

Confrontation

Let us know from the example 4-phenoxy benzamidine of Example D.25.2, ^ [(⑼ + 瓶 叫小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] _2_ (amino) ethyl ] _ Hydrochloride Q g, 17¾ mol, 1 eq) dissolved in anhydrous dichloromethane (30 ml) and added N-methyl-morpholine (0.2 g, 18.8 mmol) , U equivalent). The solution was cooled at 0-5 C, and phenyl isocyanate (0.22 g '17.7 A: Moore' 1.1 equivalent) in methane (ml) was added. Mix the mixture at 0-5. 〇 Stir for 1 hour. The solution was washed with a 2% solution of sodium chloride (50 ml), dried over anhydrous sodium sulfate, and evaporated under vacuum. The crude was suspended in ether (20 mL), stirred for 2 hours, filtered, and under vacuum at 50 ° C. It was dried at 0 ° C to obtain a white powder. Yield: 74.3%, 0.84 g.

Analytical data: melting point 143-145 ° C iHNMRCDMSO ^) ·· 8.9 (lH, d); 8.75 (lH, s); 8.59 (lH, d); 7.95 (2Η, d); 7.45 (2H, t) ; 7.35 (2H, d); 7.2 (3H, m); 7.1 (4H, m); 6.9 (lH, m); 6.25 (lH, t); 4.65 (lH, m); 4.10 (lH, d); 3.65 (lH, m); 3.4 (lH, m); 2.6 (lH, m); 2.2 (lH, m); 2.1 (lH, m); 1.85 (2H, m); 1.65 (2H, m), 1 · 3 (3H, m); (6H, d); 0.80 (9H, t). Example D.23

4-Butylbenzidine,] ^ _ [(18) -1-[[((111) -1 _ [(3 &amp; 8 batches, 68,7 &amp; 11) _hexagon-3 &amp;, 5,5 -Trimethyl_4,6_methylalkyl-1,3,2-benzodioxofluoren-2-yl + 3-fluorenylbutyl I 95014 -191-200529810 amino 1 carbonyl] -2- (4-methylbenzenesulfonylureido) ethyl] _

Example 4-Butylbenzamide, N is cut off from Example D.17.-Serving small • [(3aS, 4S, 6S, 7aR &gt; Hexahydro-3otrimethyl 4,6-methane Yl, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] quinyl] -2- (aminoethyl) _hydrochloride (56 mg , 1.07 mmol, 1 equivalent) was dissolved in anhydrous digas methane (20 ml), and the solution was cooled at 0-5 C. N-methyl-morpholin (0125 ml, 1.129 pen moles) was added. '1.1 equivalent); 4-Toluene isocyanate with isocyanate (0.22 g, 112 mmol, U equivalent), and the mixture was stirred at room temperature for 2 hours. The mixture was treated with #nucleic acid solution 2% ( 20 ml) and 2% solution (25 ml) of sodium gasification. The organic layer was dried over anhydrous sodium sulfate, dried, and evaporated under reduced pressure 9. The crude material was dissolved in ethyl acetate (40 ml), The solvent was evaporated. The crude material was suspended in n-hexane (20 ml), stirred at room temperature for 1 hour, filtered, and dried under vacuum at 50 ° C to obtain a white powder. Yield 75.6%, 0.55 G. Analytical data: melting point 168-170 ° C. IHNMR ^ DMSO-dG): 10.8 (lH, s); 8.75 (lH, d); 8.35 (lH, d); 7.75 (4H, m); 7.35 (5H, m); 6.65 (lH, t); 4.5 (lH, t); 4.1 ( lH, d); 3.5 (lH, m); 3.25 (lH, m); 2.65 (3H, m); 2.3 (3H, d); 2.2 (lH, m); 2.1 (lH, m); 1.80 (2H , M); 1.65 (4H, m), 1.3 (12H, m); 0.8 (12H, m). 95014 -192- 200529810 Example D.24 Synthesis of other compounds according to Example D.18 -D.23 procedure, the following compounds can be obtained through examples D.17 or D.25 intermediates and appropriate commercially available carboxylic acids, fluorenyl halides, sulfonyl halides, isocyanates, sulfonyl isocyanates , Or made by reacting with the compounds of Examples G.14, G.15 and G.16. All the compounds obtained have been identified by 1 H-NMR characteristics. D.24.1 I Palmarity-0 ^? ^ 0 Φ F Chemical name: Decylamine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3 ^ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Carbonyl] -2- [4-fluoro-benzenesulfonamide] ethyl]. D.24.2. krH KD &lt; Chemical name: Decylamine, N-[(lS) -l-[[[(lR) -H (3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-trimethyl- 4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(4-sulfonamidobenzene Group) carbonylamido] ethyl] -Analytical data: NMR (DMSO-d6): 8.8 (1H, d); 8.55 (1H, t); 8.35 (1H, d); 7.92 (2H, d); 7.88 (2H, d); 7.45 (2H, s); 4.6 (1H, t); 3.5 (2H, m); 2.2 (1H, m); 2.1 (2H, m); 2.05 (1H, m); 1.8 (2H, m); 1.6 (2H, m); 1.45 (3H, m); 1.25 (24H, m); 1.65 (4H, m), 0.80 (12H, m). Melting point 1780-1810C. D. 24.3 people Chemical name: 4-butylbenzamide, &gt; 1-[(13) -1-[[[(111) 小 [(3 &amp; 343,68,7 &amp; feet) -hexagon-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl-]-3-methylbutyl] amino] carbonyl] -2- (ethyl Fluorenylamino) ethyl] -D.24.4] '= 0 0 Chemical name: 4-butylbenzylamine, N-[(lS) -l-[[[((lR) -l-[(3aS, aS, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl-]-3-fluorene Butyl] amino] carbonyl] -2- (panesulfonamido) ethyl]-950 14 -193- 200529810

D.24.5 O ^^ NH s Chemical name: 4-butylbenzamide, ， [(13) 小 [[[((111) -1-[(3 &amp; 343,63 &gt; 11) -hexahydro-3a , 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2- ( Propylureido) ethyl] -Analytical data:! H NMR (DMSO-d6): 8.9 (1H, s); 8.6 (1H, d); 7.8 (2H, d); 7.25 (2H, d); 6.2 (1H, t); 6.05 (1H, t); 4.5 (1H, t); 4.05 (1H, t); 3.4 (1H, m); 2.9 (1H, m); 2.65 (2H, t); 2.2 ( 1H, m); 2.0 (1H, m); 1.8 (2H, m); 1.65 (4H, m); 1.2 (15H, m), 0.80 (16H, m). D. 24.6 I Benzene 〇xa κ Chemical name: 4-Butylbenzamide, &gt; ^ [(13) -1-[[[(111) -1-[(3 &amp; 343,63,7 &amp; 11) -hexagon-3a, 5 , 5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2-[( 4-methylphenyl) carbonylamino] ethyl]-D.24.7 Chemical name: 4-butylbenzylamine,] ^-[(13) -1-[[[((111 &gt; * 1 _ [( 333, &amp; 3,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxoborofluorene-2- + 3-methylbutyl] amino] carbonyl] -2-[(l, l-dimethylethyl Carbonyl) amino] ethyl] -Analytical data: lH NMR (DMSO-d6): 8.8 (1H, s); 8.25 (1H, d); 7.8 (2H, d); 7.3 (2H, d); 6.9 ( 1H, t); 4.65 (1H, t); 4.1 (1H, d); 2.65 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H, m); 1.6 (4H , m); 1.3 (20H, m); 0.9-0.80 (12H, m). D.24.8 Paraparity &lt; Chemical name: 4-butylbenzamide,] ^-[(13) -1- [[((11〇 小 [(3 冱 3,43,63,7wang11) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzo Dioxobenzo-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-busphen-2-ylcarbonyl) amino] ethyl]-D.24.9 〇r1 human f 〇 Λο The chemical name of palmitate: Decylamine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3 &amp;, 5,5-triamidine -4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-[(fluorene-2- Carbonyl) amino] ethyl] -D.24.10 Paraquatic chemical name: 4-butylphenylhydrazine, &gt; 4 (13) -1-[[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl]- 3-methylbutyl] amino] carbonyl] -2- (hexanone amine ) Ethyl] -

95014 -194- 200529810

D.24.11 Chemical name: 4-Butylbenzidine, &gt; 1-[(13) -1-[[[(111) -1- [3 &amp; 3an 3,63,7 &amp; 11] -six Hydrogen-3a, 5,5-trifluorenyl-4,6-methylalkyl 1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] several groups ] -2- (Cyclopropylcarbonylamino) ethyl]-D.24.12 I Parapetical chemical name: 4-butylphenylhydrazine, 泎 [(13) -1-[[[(111)- 1-[(333,43,63,7 &amp; foot) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 -Yl] -3-methylbutyl] amino] carbonyl] -2- (3-phenyl-ureido) ethyl]-D.24.13 ct ° Chemical name: 4-butylbenzylamine, ^ 4 (18) -1-[[[(111) 小 [(3 &amp; 3,43,63,7311) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(N-methyl-2-pyrrolylcarbonylamido) ethyl]- D.24.14 HN, ice chemical name: 4-butyl benzamidine, N-[(lS) -H [[(lR) -l- [3aS, aS, 6S, 7aR] -hexagon-3a, 5 , 5-trifluorenyl-4,6 · fluorenylalkyl 1,3,2-benzodioxofluoren-2-yl-]-3-fluorenylbutyl] amino] carbonyl] -2- [ (3,4-dimethoxyphenyl) acetamido] ethyl]- D.24.15 | Palmar οΛ0 Chemical name: 4-Butylbenzidine, team [(18) -1-[[[(111) 4-[(3 冱 3,43,63,7 &amp; 1〇 -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoborohydrin-2-yl] -3-fluorenylbutyl] amino] Carbonyl] -2- (nicotinylketoamino) ethyl]-D.24.16 γ 〇Λα / 〇 //, νη2 Chemical name: 4-butylphenylhydrazine, meaning [(13) 小 [[[ (1 trans) small 〇3, &amp; 3,63,7 &amp; 11] -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl 1,3,2-benzodioxane Fluoren-2-yl-]-3-methylbutyl] amino] carbonyl] dong [(4-ruthanthenylamino) phenylfluorenyl] ethyl]-95014 -195- 200529810

D.24.17 HN, ~ V \ Chemical name: 4-butylbenzimidamine, swimming [(13) 小 [[[(111) 小 | &gt; 3 ^, 63 &gt; 11] -hexahydro-3a, 5 , 5-trimethyl-4,6-methylalkyl1,3,2-benzodioxolanyl + 3-methylbutyl] amino] carbonyl] -2-[(1Η-tetrazole 5-Alkyl-acetamido) ethyl) -Analytical data: 1E NMR (DMSO-d6): 9 (1H, s); 8.55 (1H, d); 8.5 (1H, br); 7.75 (2H, d); 7.3 (2H, t); 4.6 (1H, t); 3.4 (2H, m); 2.65 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H, m ); 1.6 (4H, m); 1.3 (14H, m); 0.9-0.80 (12H, m). D.24.18 I Parapetical chemical name: 4-butylbenzamide, 1 ^-[(13 ) -1-[[[((111) -1-[(3 &amp; 3, &amp; 3,63,7 &amp; 11) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] carbonyl] -2-[(4-fluorenylsulfonylphenyl) carbonylamino ] Ethyl]-D.24.19 I Palmarity 0 Sh 0 \ IX Chemical name: Decylamine, N-[(lS) -l-[[[(lR) -H (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-l, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Carbonyl] -2- (nicotinylketoamino) ethyl]-D.24.20 I palsy 〇x ^ &gt; Ν, ί Chemical name: 4-butylphenylhydrazine, N-[(1S) -H [[(1R) -H (3aS, aS, 6S, 7aR) -six Argon-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl-]-3-fluorenylbutyl] amino] Carbonyl] -2-[(4- (2Η ,, azol-5-yl) phenyl) carbonylamino] ethyl] _D.24.21 Para-hN; Ca 〇Λχ &gt; Chemical name: 4-butylbenzene Formamidine, N-[(1S) -1-[[[(1R) 小 [(3 &amp; 3, &amp; 3,63,7ug11) -hexahydro-3a, 5,5-trisyl- 4,6-fluorenyl-1,3,2-benzodioxoline-2-yl + 3-methylbutyl] amino] carbonyl] -2-[(l-isopurazol-5 -Yl) -pyridylamino] ethyl]-

95014 196- 200529810

D.24.22 o palms. ό II Ν Chemical name: 4-butylbenzamide, N-[(lS) -l-[[[((lR) -l-[(3aS, aS, 6S, 7aR) -hexahydro-3a, 5 , 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2-[(4 -Cyanophenyl) sulfonamido] ethyl]-Analytical data: 1E NMR (DMSO-d6): 8.6 (1H, d); 8.3 (1H, d); 8.1 (1H, t); 8.02 ( 2H, d); 7.98 (2H, d); 7.8 (2H, d); 7,25 (2H, d); 4.6 (1H, t); 4.15 (lH, d); 3.2 (2H, m); 2.2 (1H, m); 2.1 (1H, m); 1.8 (2H, m); 1.6 (4H, m); 1.3 (12H, m); 0.9-0.80 (12H, m). D.24.23 〇 today &gt; Ν \ Chemical name: 4-butylbenzamide,] ^ [(13) -1-[[[(111) -1-[(333, &amp; 3,63,7 &amp; 11) -hexahydro- 3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2 -[(l-methyl-1H-imidazole-4-) sulfonamido] ethyl]-D.24.24 0 = 1 ^ ° t &gt; Chemical name: 4-butylbenzidine, 1 ^ [ (13) -1-[[[((111) -1-[(3 &amp; 3, 3,63,7 &amp; 11) -hexahydro-3a, 5,5-difluorenyl-4,6-methane -1,3,2-benzyldioxo-wooden-2-yl + 3-fluorenylbutyl] amino] carbonyl] -2-[(2-edge Phenyl) sulfonylamino] ethyl] -D.24.25 X) Chemical name: 4-butylbenzylamine, swimming [(18) 小 [[[(111) 小 [(3rd 3, &amp; 3,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl-]-3 -Methylbutyl] amino] carbonyl] -2- (6-morpholine-4-nicotinylamidoamino) ethyl]-D.24.26 Chemical name: 4-butylphenylhydrazine, N -[(1S) 小 [[[(111) 小 [(3 &amp; 3, &amp; 3,63,7 &amp; 11) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl- 1,3,2-benzodioxoline-2-yl-]-3-methylbutyl] amino] carbonyl] -2- (2-pyridine-4-pyrimazolecarbonylamino) ethyl ]-

95014 197- 200529810 D.24.27

Chemical name: 4-butylbenzamide,] ^-[(13) -1-[[[(1feet) -1-[(3 &amp; 3,33,63,7 &amp; and) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] carbonyl] 2- (4-fluorenylphenylureidosulfonamido) ethyl] -Analytical data: lH NMR (DMSO-d6): 10 (1H, br); 8.8 (1H, s); 8.4 (2H , d); 7.8 (2H, d); 7.3 (2H, d); 7.25 (2H, d); 4.6 (1H, t); 4.2 (lH, d); 2.65 (3H, m); 2.2 (4H, m); 2.0 (1H, m); 1.8 (2H, m); 1.6 (4H, m); 1.3 (12H, m); 0.9-0.80 (12H, m) ._ D.24.28

Parapetical chemical name: 4-benzyloxybenzidine, N-[(1 S) -1-[[[(1 R &gt; H (3 aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-Dimethyl-4,6-methylalkynyl-1,3,2-phenylhydrazinobiol-2-yl] -3-methylbutyl] amino] carbonyl] -2- [(Methoxycarbonylamido) ethyl] -D.24.29 Palmarity

, FjJH Chemical name: 4-phenoxybenzidine, [[15) -1-[[[(111) -1-[(333,48,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2 · benzodioxoline-2-yl] -3-fluorenylbutyl] amino] carbonyl] _2- [4 _Fluoro-sulfenazamide] ethyl]-D.24.30

Chemical name: 4-phenoxybenzimidamine, 1 ^ [(18) 小 [[[((1 尺) 小 [(33343,63,7 &amp; 11) -hexahydro-3a, 5,5-dimethyl -4,6-methylalanyl-1,3,2-benzodioxocarbox-2-yl-]-3-fluorenylbutyl] amino] carbonyl] _2 _ [(2,5-di Methyl-2'-pyrazole) carbonylamino] ethyl] -D.24.31

Chemical name: 4-phenoxybenzidine, N-[(1S) 小 [[[(111) 小 [(333,43,63,7 &amp; 11) -hexahydro-3 \ 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2- (4-phenylbenzene Amidino) ethyl) -D.24.32

Chemical name: 4-butyl benzamidine, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43,633trans) -hexahydro-3a, 5,5-trifluorenyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2_ (4-phenylbenzidine (Yl) ethyl]-95014 -198- 200529810 D.24.33% Chemical name: 4-butylbenzamide, &gt; 1-[(13) -1-[[[(111) -1-[(333 , 43,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 -Methylbutyl] amino] carbonyl] -2- (3-phenylpropynamidinylamino) ethyl]-D.24.34 HO ', N〃 Chemical name: 4-butylphenylhydrazine, 1 ^ [(13) -1-[[[(111) -1-[(3 &amp; 3, &amp; 8,63,7 & foot) -hexahydro-3a, 5,5-trimethyl-4, 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] amino] carbonyl] -2- (2-hydroxy-3-nicotinylfluorenylamine ) Ethyl] -D.24.35 Chemical name: 4-butylbenzamide, &gt; 1-[(13) -1-[[[(111) -1-[(3 冱 343,63 &gt; 11 ) -Hexargon-3 &, 5,5-Difluorenyl-4,6-methylalanyl-1,3,2-benzyldioxofluoren-2-yl-]-3 -methylbutyl ] Amine] carbonyl] -2- (D-pyramidamine ) Ethyl] -Analytical data: lR NMR (DMSO-d6): 9.85 (1H, d); 8.3 (1H, d); 8.1 (1H, t); 7.8 (3H, m); 7.3 (2H, d) ; 4.7 (1H, t); 4.15 (1H, d); 3.9 (1H, m); 3.5 (2H, m); 2.65 (3H, m); 2.2 (2H, m); 2.0 (3H, m); 1.8 (3H, m); 1.6 (4H, m); 1.3 (11H, m); 0.9-0.80 (12H, m). D.24.36 Chemical name: 4-butylphenylhydrazine,] ^-[( 18) -1-[[[((1 ^ &gt; 1-[(3 &amp; 3 ^ 3,63,7 &amp; 11) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl -1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] carbonyl] -2- (1-methanesulfonyl-hexahydropyridine-4- Carbonylamino) ethyl] -D.24.37 I Para-HN ^^ O Chemical name: Decylamine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S , 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] Amine] carbonyl] -2_ (3-phenyl) ethyl]-95014 199- 200529810 D.24.38 Chemical name: Decylamine, N-[(lS) -l-[[[(lR) -l- [ (3aS, aS, 6S, 7aR)-T kNHH hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzobis | H \ _V \ ^^ 0 Oxyborin-2-yl + 3-fluorenylbutyl] amino] carbonyl] -2- ( Acetylamino) ethyl]-Example D-25 Synthesis of Other Compounds Following the procedure of Example D17, the following compounds can be obtained from Examples D.16.8 and D.16.9

Compounds start to make. Example Structural Chemical Name and Analytical Data Number D.25.1 Equivalent | Chemical Name: Decylamine, N-[(1S) -H [[(1R) -H (3 aS, aS, 6S, 7aR) -hexahydro -3a, 5,5-trimethyl-4,6-methylethenyl-1,3,2-benzodioxoline-2-yl-]-3-fluorenylbutyl] amino] carbonyl ] -2-Amino] ethyl] hydrochloride CIH analysis data: lH NMR (DMSO-d6): 8.4 (1H, d); 8.25 (1H, d); 8.15 (3H, br s); 4.58 ( 1H, m); 4.2 (1H, m); 3.1 (1H, m); 2.9 (1H, m); 2.8 (1H, m); 2.4 (4H, m); 1.9 (1H, m); 1.85 (1H , m); 1.65 (2H, m); 1.50 (2H, m); 1.35 (1H, m); 0.85 (12H, m). D.25.2 I Opposition α ° χν &quot; Λν ^ ν Chemical name: 4 -Phenoxybenzimidamine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5-trifluorenyl -4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-methylbutyl] amino] carbonyl] -2- (amino) ethyl]- Hydrochloride CIH analysis data: lH NMR (DMSO-d6): 8.72 (1H, d); 8.54 (1H, d); 7.45 (2H, t); 7.22 (1H, t); 7.05 (4H, m); 4.8 (1H, m); 4.21 (1H, d); 3.25 (1H, m); 3.15 (1H, m); 2.8 (1H, m); 2.25 (1H, m); 2.05 (1 H, m); 1.9 (1H, t); 1.82 (1H, m); 1.65 (2H, m); 1.28 (3H, s); 1.22 (3H, s); 0.85 (9H, m). Example D. 26 4-Butylbenzamide, 乂 [(111) _1-[[[(111) _1 _ [(3,48,68; ^ 11) -hexahydro-32,5,5-trimethyl- 4,6-methylalkyl-1,3,2-benzodioxoline-2-yl] -3-fluorenylbutyl] amine 95014 -200- 200529810 group] carbonyl] -2-[(4- Methylbenzyl) amino] ethyl]

For palmity, the same procedure is used to prepare the compound of Example D.17, the intermediate 4-butylphenylhydrazine, 1 ^ [(111) small [[[(111) -1-[(3 略 43 , 68,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl 4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3- Methylbutyl] amino] carbonyl] -2- (aminoethyl) -hydrochloride is prepared using D-aspartin as a starting material. Then, according to the procedure described in Example D.18, the intermediate described below was reacted with 4-methylbenzoic acid to obtain the title compound. iHNMRCMeOD-dA: 8.88 (2H, d); 8.45 (2H, m); 7.8 (2H, d); 7.7 (2H, d); 7.35 (2H, m); 7_25 (2H, d); 4.75 ( 1H, m); 4 · 1 (1H, d); 3 · 8 (1H, m); 3.65 (2H, m); 2.65 (3H, m); 2.2 (lH, m); 2.1 (lH, m) 1.8 (2H, m); 1.6 (4H5 m); 1.3-1.1 (2H3 m); 0.9-0.80 (14H, m). Example El Dihydroxyborane, [(1R) -1- [丨 (2S) -5 _ [[Iminino (sonylamino) methyl] amino1-2-[(2-Tetramethyl) amino] small ketopentyl] amino 3-methylbutyl I -

95014 -201-200529810 will be described in Example D.1.1, which amines, which S &gt; 1 ^ 1RH Galois 7 is called hexahydro-3a, 5,5_trimethyl-4,6_methylalkyl ", 3 &gt; benzene And dioxoborohydride] each methylbutyl] · amino] carbonyl] -4 _ [[iminoamidoamino) methyl] amino] butyl]-(564 pen, 0. 90 mol), 孓 methylpropyldihydroxyborane 卩 22 mg, 2.19 耄 mol) and 4N hydrogenated dioxolane solution (225 μl) in methanol · hexane 40: 60 uneven The mixture in the mixture (10 ml) was stirred at room temperature for 4 hours. Hexane (4 ml) was added, the mixture was stirred for a while, and the hexane layer was removed. Fresh hexane (5 ml) and 2-methylpropyldihydroxyborane (100 mg, 0.99 mmol) were added, and the mixture was stirred at room temperature for 3 hours. The hexane layer was removed and the methanol phase was washed with hexane (2x5 ml). The residue obtained after concentrating the methanol phase was purified by silica gel column chromatography, and firstly dissolved with ethyl acetate and then with a 40:40:20 acetone: methanol · · hexane mixture. The product was redissolved in a mixture of ethyl acetate (250 ml) and methanol (6 ml) and the organic phase was washed with water (2 x 25 ml), dried over sodium sulfate, and concentrated. The residue was dried under vacuum at 80 ° C for 3 hours to obtain the product as # white solid (280 mg, 64% yield).

170-190 ° C 1H NMR (DMSO-d6): 8.76 (1¾ m); 8.51 (2H, br); 8.09-7.09 (5H, m); 7.88 (2H, bio; 7.60 (2H, br); 4.67 (lH, m); 3.17 (2H, m); 2.58 (lH, m); 1.81 (2H5m); 1.56 (3H5m); 1.38-1.11 (4H, m); 0.83 (lH, m); 0.81 (1H5 m); 0.74 (3H, d, J = 6.4); 0 · 74 (3H, d, J = 6.4). Calculated value of elemental analysis: C 54.33% H6.43% N 17.28% B 2.22% Measured value C 54.87% H 6.64% N 17.00% B 2.12% Other compounds made basically according to the above experimental procedures are reported in Tables 95014-202- 200529810 El. Table El Example Structure Number E.1.1

'^ 0 Chemical name and analytical data E.1.2

E.1.3

95014 E.1.4

Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[((2Ε) -3-ethyl Oxoyl-l-oxoprop-2-fluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 7.07 (1H , d, J = 15.6 Hz); 6.74 (1H, d, J = 15.6 Hz); 4.64 (1H, dd, J = 6.3, 8.1); 4.25 (2H, q, J = 7.1); 2.75 (1H, t , J = 7.4); 2.0-1.6 (5H, m); 1.34 (2H, m); 1.31 (3H, t, J = 7.1); 0.92 (6H, d, J = 6.6) ._ Chemical name: Dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(24-chlochyl) amino] -1 -Ketopentyl] amino] -3-fluorenylbutyl] Analytical data: 1H-NMR (DMSO-d6): 9.18 (1H, br); 8.96 (1H, d, J = 8.2); 8.87 (1H , d, J = 2.4 Hz); 8.76 (2H, m); 8.51 (1H, br); 8.3-7.5 (2H, br); 4.63 (1H, m); 3.13 (2H, m); 2.53 (1H, m); 1.9-1.1 (7H, m); 0.73 (6H, d, J = 6.6) .___ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) fluorenyl] amino] -2-[(4-butylphenylfluorenyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data : LH-NMR (DMSO-d6): 8.68 (1H, d, J = 2.5 Hz); 8.51 (1H, br); 8.48 (1H, d, J = 7.8 Hz); 8.3-7.5 (2H, br); 7.80 (2H, d, J = 8.1); 7.27 (2H , d, J = 8.1 Hz); 4.59 (1H, m); 3.15 (2H, m); 2.61 (2H, t, J = 7.7); 2.54 (1H, m); 1.9-1.1 (11H, m); 0.89 (3H, t, J = 7.3); 0.77 (3H, t, J = 6.8); .0.74 (6H, d, J = 6.6) ._ Chemical name: Dihydroxyborane, [(lR) -l- [[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(2-fluorenyl) amino] -1-ketopentyl] amino ] -3 · methylbutyl] Analytical data: 1H-NMR (DMSO-d6): 8.77 (1H, br); 8.76 (1H, d, J = 8.0); 8.51 (1H, br); 8.50 (1H, s); 8.0 (4H, m); 8.3-7.5 (2H, br); 7.6 (2H, m); 4.67 (1H, m); 3.17 (2H, m); 2.57 (1H, m); 1.9-1.1 (7H, m); 0.73 (6H, d, J = 6.6).

203-200529810

E.1.5 1 palmity \ χ η r Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amine ] -2-[(3- (1,3-dihydro4,3-diketo-2H-isofluorindol-2-yl) -1-ketopropylamino) -1-ketopentyl ) Amino) -3-methylbutyl) o- ~. Analytical data: 1H-NMR (DMSO-d6): 8.59 (1H, br); 8.43 (1H, br); 8.27 (1H, d, J = 7.9 Hz); 7.82 (4H, m); 8.2-7.5 (2H , br); 4.31 (1H, m); 3.77 (2H, m); 3.08 (2H, m); 2.51 (3H, m); 1.7-1.1 (7H, m); 0.78 (6H, m) .E. 1.6 I-pairs, human γΟΗ 0, Η OH \ χ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino)) 曱[Amino] amino] -2-[[2- (2-methoxyethoxy) ethylfluorenyl] amino] -1-ketopentyl] amino] -3-fluorenylbutyl], HC1 Salt N ', NH Hc, H o Human analysis data: 1H-NMR (MeOH-d4): 4.65 (1H, dd, J = 6.1, 8.6 Hz); 4.04 (2H, s); 3.70 (2H, m); 3.60 (2H, t, J = 4.04) 3.42 (3H, s); 3.30 (2H, t, J = 6.9); 2.75 (1H, t, J = 7.5); 2.0-1.6 (5H, m); 1.34 ( 2H, m); 0.92 (6H, d, 5 = 6.6). E.1.7 Q jf H cA〇 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) fluorenyl] amino] -2-[(2-butoxyethylfluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 4.65 (1H, dd, J = 6.1, 8.6 Hz); 3.98 (2H, s); 3.54 (2H, t, J = 6.6); 3.28 (2H, t, J = 6.9) ; 2.77 (1H, t, J = 7.6); 2.0-1.3 (11H, m); 0.95 (3H, t, J = 7.58); 0.92 (6H, d, J = 6.6). E.1.8 I confrontation . ~ Γ ％ ^ γ0Η ° Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [ [2- [2- (2-Methoxyethoxy) ethoxy] ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] O '^ 0 Analytical data: 1H-NMR (MeOH-d4): 4.66 (1H, dd, J = 6.0, 8.8 Hz); 4.06 (2H, AB q, J = 15.7); 3.7 (6H, m); 3.58 (2H, m ); 3.37 (3H, s); 3.29 (2H, t, J = 6.9); 2.75 (1H, t, J = 7.7); 2.0-1.6 (5H, m); 1.34 (2H, m); 0.92 (6H , d, J = 6.6). E.1.9 I palladium ί '1 Η {〇Η \ τ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[ Imino (nitroamino) methyl] amino] -2-[[2- (ethylamido) ethylamido] amino] -1-ketopentyl] amino] -3- 曱Analytical data: 1H-NMR (MeOH-d4): 4.61 (1H, dd, J = 5.7, 8.9 Hz); 3.86 (2H, s) ; 3.37 (3H, s); 3.30 (2H, t, J = 7.0); 2.75 (1H, t, J = 7.7); 2.01 (3H, s); 2.0-1.6 (5H, m); 1.33 (2H, m); 0.92 (6H, d, J = 6.6).

95014 204- 200529810

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[4- (methoxy Carbonyl) butylammonyl] amino] small_ylpentyl] amino] _3-methylbutyl] Analytical data: lH NMR (DMSO-d6): 8.50 (1H, br); 8.44 (1H, d, J = 5.6 Hz); 8.17 (1H, d, J = 7.5); 7.92 (2H, br); 4.37 (1H, m); 3.58 (3H, s); 3.14 (2H, m); 2.57 (1H, m); 2.30 (2H, t, J = 7.3); 2.19 (2H, t, J = 7.5); 1.75 (2H, quintet,: F = 7.3); 1.71 (1H, br); 1.64-1.39 (4H, br); 1.23 (2H, m); 0.86 (2H, m); 0.82 (3H, d, J = 6.4); 0.81 (3H, d, J = 6.4). _ Chemical name: Dihydroxyborane, [( lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(2- (naphthalene-2-yloxy) ethenyl) Amine] small ketopentyl] amino] -3-fylbutyl] Analytical data: lHNMR (DMSO-d6): 8.81 (1H, br); 8.51 (1H, br); 8.40 (1H, d, J = 7.5 Hz); 7.88 (2H, br); 7.83 (2H, m); 7.75 (1H, m); 7.44 (1H, m); 7.35 (1H, m); 7.26 (2H, m); 4.69 ( 2H, m); 4.51 (1H, m); 3.12 (2H, m); 2.60 (1H, m); 1.78 (1H, m); 1.73-1.39 (3H, m); 1.39-1.11 (3H, m) ; 0.80 (6H, m) ._ Chemical name: two Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(3-pyridin-2-yl- Propionyl) amino] small ketopentyl] amino] fluorenylbutyl] Analytical data:! H NMR (DMSO-d6): 8.65 (1H, br); 8.49 (1H,

br); 8.20 (1H, d, J = 8.2 Hz); 7.86 (2H, br); 7.27 (1H, dd, J = 4.9, J = 0.9); 6.91 (1H, dd, J = 5.1, J = 3.4 ); 6.84 (1H, m); 4.38 (1H, m); 3.11 (2H, m); 3.02 (2H, m); 2.56 (1H, m); 2.50 (2H, m); 1.69 (1H, m) ; 1.64-1.35 (4H, m); 1.27 (1H, m); 1.20 (1H, m); 0.82 (3H, d, J = 6.4); 0.81 (3H, d, J = 6.4) ._ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2- [2- (2-Gaphenyl)) Acetyl] amino] -3-fluorenylbutyl] HC1 salt analysis data: lH NMR (DMSO-d6): 8.69 (1H, br); 8.51 (1H, br); 8.41 (1H, d, J = 7.9 Hz); 7.87 (2H, br); 7.40 (1H, m); 7.32 (1H, m); 7.26 (2H, m); 4.42 (1H, m); 3.66 (2H, m); 3.14 (2H, m); 2.60 (1H, m); 1.73 (1H, m); 1.68-1.40 (4H, m); 1.26 (2H, m); 0.83 (3H, d, 3 = 6.4); 0.82 (3H, d, J = 6.4).

95014 205-200529810

E.1.14 _O ^ TnHX ^ h Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [ (1-fluorenyl-4- (1-butylhexamidine-benzyl) butyl) amino] -1-ketopentyl] amino] -3-methylbutyl] crN々o Palm analysis data: lH NMR (DMSO-d6): 8.60 (1H, br); 8.50 (1H, br); 8.10 (1H, br); 8.00 (2H, br); 4.36 (1H, m); 3.13 ( 2H, br); 2.86 (2H, br); 2.50 (1H, m); 2.27 (1H, br); 2.11 (2H, m); 1.76-1.34 (11H, m); 1.34-0.98 (11H, m) ; 0.87 (3H, t, J = 7.1 Hz), 0.82 (3H, d, J = 6.4); 0.81 (3H, d, J = 6.4). E.1.15 I Chiral person-day-OH. "H 1 f Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (nitroamino) methyl] amino] -2-[(1 -Octanesulfonyl) aminoamino-M-pentyl] amino] -3-methylbutyl], HC1 salt H-CI S ^ NH Η (Λ. Analytical data · lH NMR (DMSO-d6) : 8.80 (1H, br); 8.50 (1H, br); 7.87 (2H, br); 7.52 (1H, d, J = 8.6 Hz); 3.92 (1H, m); 3.15 (2H, m); 2.94 ( 2H, t, J = 7.7); 2.62 (1H, m); 1.75-1.43 (7H, m); 1.38-1.31 (4H, m); 1.24 (8H, s); 0.92-0.75 (9H, m). E.1.16 I-paraben 〇, ΝΗ ° \ χ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-[(4-methylbenzylidene) amino]] -2-[(Decanoylamino)]-1-ketopropyl] amino] -3-methylbutyl] Analytical data lH NMR (CD30D): 7.73 (2H, d, J = 8.0 Hz ); 7.28 (2H, d, J = 8.0); 4.78 (1H, t, J = 6.5); 3.82 (1H, dd, J = 6.9, 13.5); 3.61 (1H, dd, J = 6.9, 13.5); 2.74 (1H, m); 2.39 (3H, s) f2.24 (2H, t, J = 7.4); 1.6-1.15 (17H, m); 0.89 (6H, m); 0.80 (3H, d, J = 6.5). E.1.17 I palmar ^ human γ〇Η Chemical name: Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2-[(decanoyl) Amine] Minor Analytical data: lH NMR (DMSO-d6): 8.58 (1H, br); 7.70 (1H, d, J = 8.6 Hz), 4.93 (1H, br); 4.31 (1H, dd, J = 4.0, 8.6); 3.96 (1H, m); 2.56 (1H, m); 2.18 (2H, m); 1.60 (1H, m); 1.49 (2H , m); 1.35-1.15 (14H, m); 1.03 (3H, d, J = 6.4); 0.83 (9H, m). E.1.18 1 pair of chemical names: dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[[10- (l, 3-diketo-1,3-dihydro-isoamido-2-yl) -decylenyl] Amino] small ketobutyl] amino] -3-methylbutyl] Analytical data: lH NMR (DMSO-d6): 8.55 (1H, br); 7.84 (4H, m); 7.69 (1H, d , J = 8.4 Hz), 4.94 (1H, d, J = 5.4); 4.30 (1H, dd, J = 4.0, 8.6); 3.95 (1H, m); 3.55 (2H, m); 2.55 (1H, m ); 2.17 (2H, m); 1.65-1.35 (5H, m); 1.3-1.1 (12H, m); 1.02 (3H, d, J = 6.4); 0.83 (9H, m).

95014-206- 200529810 Other compounds made according to the procedure described above for Example E.1 are reported in Table E-1A.

Table E-1A Example No. Structure Chemical name and analysis data E.1.19

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[((RS) -10 -Cyano-2-cyclopentyldecanoyl) amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: 1H-NMR (MeOH-d4): 4.57 (1H , m); 3.29 (2H, m); 3.20 (2H, m); 2.76 (1H, t, J = 7.5Hz); 2.43 (2H, t, J = 7.1); 2.05 (1H, m); 2.0- 1.1 (11H, m); 0.93 (6H, d, J = 6.6) ._

E.1.20 E.1.21 E.1.22

Confrontation

Opposition

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(10- (l, 3-dihydro-1,3-diketo-2H-isoindone-2-yl) -1-¾yldecyl)-) amino] -1--ylpentyl] amino] -3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 7.82 (4H, m); 4.52 (1H, m); 3.66 (2H, t, J = 7.3); 3.27 (2H, m ); 2.75 (1H, m); 2.24 (2H, t, J = 7.3 Hz); 1.9-1.2 (20H, m); 0.91 (6H, d, J = 6.6) ._ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(2-cyclopentyl-10- (1,3- Dihydro-1,3-diketo-2H-isoamido-2-yl) -1-ketodecyl)-) amino] -1-ketopentyl] amino] -3-methyl Butyl] Analytical data: 1H-NMR (MeOH-d4): 7.82 (4H, m); 4.57 (1H, m); 3.66 (2H, t, J = 7.3); 3.28 (2H, m); 2.75 (1H , m); 2.05 (1H, m); 2.0-1.1 (30H, m); 0.91 (6H, two d, J = 6.6) .___ Chemical name: Dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[[7- (fluorenylcarbonyl) heptanyl] aminofluorenylpentyl] amino] -3-methylbutyl] Analytical data: lH NMR (DMSO-d6): 8.60 (1 H, d, J = 8.4 Hz); 8.50 (1H, br); 8.06 (1H, d, J = 7.9); 7.92 (2H, br); 4.36 (1H, m); 3.58 (3H, s); 3.13 (2H, m); 2.55 (1H, m); 2.28 (2H, t, J = 7.5); 2.12 (2H, m); 1.69 (1H, m); 1.49 (7H, m); 1.24 (7H, m ); 0.81 (6H, m) ._ Other compounds made according to the procedure described above for Example El are reported in Table E-1B in 95014-207-

200529810

Table E-IB Example number Structural chemical name and analysis data E.1.23 | Counter chemical name: Dihydroxyborane, [(1R) -1-[[(2S, 3R &gt; 3-hydroxy-2-[(4 -Phenylbutylfluorenyl) amino] -1-ketobutyl] amino] -3-methylbutyl] Analytical data.'H NMR (MeOH-d4): 7.29-7.13 (5H, m); 4.53 ( 1H, d, J = 3.9); 4.21-4.14 (1H, m); 2.72 (1H, d, 1 = 7.6); 2.65 (2H, t, 1 = 7.6); 2.34 (2H, t, J = 7.5) ; 2.10-2.89 (2H, m); 1.70-1.59 (1H, m); 1.37-1.27 (2H, m); 1.21 (3H, d, J = 6.4); 0.94-0.89 (6H, m). E. 1.24 p-phenylene OH Chemical name: Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2-[(undecylaminocarbonyl) amino] -1- Ketobutyl] amino] -3-methylbutyl] Analytical data: [Η NMR (MeOH-d4): 4.43 (1H, d, J = 2.9); 4.27-4.20 (1H, m); 3.16 ( 2H, t, J = 6.9); 2.74 (1H, t, J = 7.6); 1.76-1.66 (1H, m); 1.58-1.46 (3H, m); 1.42-1.30 (26H, m); 1.25 (3H , d, J = 6.4). E.1.25. For t-Br 0 JL OHH '\ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy- 2-[(l-bromo-2-fluorenyl) aminofluoren-ketobutyl] amino] -3-fluorenylbutyl] Data: lH NMR (MeOH-d4): 8.37 (1H, d, J = 8.52); 7.99 (2H, dd, J = 8.2, J = 13.0); 7.75-7.60 (2H, m); 4.82 (1H, d , J = 4.19); 4.31-4.23 (1H, m); 2.81 (1H, dd, J = 6.10, J = 9.14); 1.77-1.64 (1H, m); 1.48-1.38 (2H, m); 1.36 ( 3H, d, J = 6.38); 1.0-0.9 (6H, m). E.1.26 The chemical name of I on Weiwei: Dihydroxyborane, [(lR) -H [(2S, 3R) -3-hydroxy- 2-[(6-Bromo-2-fluorenyl) amino] -1-l-stearylbutyl] amino] -3-fluorenylbutyl] Analytical data: ^ NMR (MeOH-d4): 8.49 (1H, s); 8.17 (1H, d, J = 1.4); 7.99 (1H, dd, J = 1.65, J = 8.66); 7.95 (2H, dd, J = 2.70, J = 8.62); 7.69 (1H , dd, J = 1.90, J = 8.77); 4.81 (1H, d, J = 4.26); 4.38-4.30 (1H, m); 2.77 (1H, t, J = 7.63); 1.71-1.59 (1H, m ); 1.40-1.33 (2H, m); 1.31 (3H, d, J = 6.39); 0.94-0.90 (6H, m).

Other compounds made according to the procedure described above for Example E.1 are reported in Table E-1C. Starting with the compounds of Examples D.8.19 and D.8.20. 208-95014 200529810

Table E-1C

Example number Structural chemical name and analysis data E.1.27 I pair of palms Γ〇Η 0 οη Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-aminomethylamidino-2 -[(Decyl) amino] -1-ketopropyl] amino] -3-methylbutyl] Analytical data: 1H-NMR (MeOH-d4): 4.76 (1H, t, J = 6.0 ); 2.58-2.52 (3H, m); 2.14-2.09 (2H, m); 1.64-1.52 (1H, m); 1.51-1.40 (2H, m); 1.30-1.12 (14H, m); 0.84-0.80 (9H, m). E.1.28 ° V w Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-aminomethylamido-2- [4-butyl (benzyl Fluorenyl) amino] small ketopropyl] amino] -3-fluorenylbutyl] Analytical data: 1H-NMR (MeOH-d4): 7.78 (2H, d, J = 8.24 Hz); 7.32 (2H , d, J = 8.22 Hz); 5.16 (1H, T, J = 6.52); 2.91 (2H, dd, J = 2.09 Hz, J = 6.53 Hz); 2.78 (1H, t, J = 7.59 Hz); 2.74 -2.66 (2H, m); 1.72-1.60 (3H, m); 1.44-1.30 (5H, m); 1.00-0.9 (9H, m). Others made according to the procedure described above for example E.1 The compounds are reported in Table E-1D, starting with the compounds of Examples D.2.9 and D.2.10. Table E_1D Example number Structural chemical name and analytical data E.1.29 I Palmarity {) k H &amp; \ Λ ^ H ^ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -2 -[(Decanoyl) amino] small keto-5-entyl-pentyl] amino] -3-methylbutyl] Analytical data: 1H-NMR (DMSO-d6): 8.56 (1H, s ); 8.07 (1H, d, J = 8.03 Hz); 5.96 (1H, t, J = 5.18 Hz); 5.38 (2H, s); 4.42-4.20 (1H, m); 3.01-2.85 (2H, m) ; 2.65-2.40 (1H, m); 2.25-2.00 (2H, m); 1.70-1.52 (2H, m); 1.52-1.40 (3H, m); 1.40-1.10 (16H, m); 0.90-0.75 ( 9H, m). 95014 209-200529810

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -2-[(4-butylbenzylidene) amino]]-1, 5--5-adenosyl-pentyl] Amine] -3-Aminobutyl] Analytical data: 1H-NMR (MeOH-d4 + DMSO-d6): 7.80 (2H, d, J = 8.08 Hz); 7.28 (2H, d, J = 8.16 Hz) ; 4.58 (1H, t, J = 7.41 Hz); 3.00 (2H, t, J = 6.72 Hz); 2.63 (2H, t, J = 7.64 Hz); 1.82-1.74 (2H, m); 1.68-1.52 ( 4H, m); 1.52-1.36 (2H, m); 1.34-1.26 (2H, m); 1.21 (2H, t, J = 7.23 Hz); 0.89 (3H, t, J = 7.35 Hz); 0.84 (6H , d, J = 6.55 Hz) ._

Example E.2 Dihydroxyborane, [(1R) Small [[(2S) _5-[[Imine (sonylamino) methyl] amino] -2-[(decylamino) amino] _1_fluorenylpentyl] amino] each methylbutyl I-

The decylamine of Example D.1, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43,63 &gt; 11) -hexahydro-3a, 5,5-trimethylamine -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Aminoamino) methyl] amino] butyl]-(77 mg, 0.12 mmol) was dissolved in Et20 (1 ml) and HC1 37% (2 ml) was carefully added at 0 ° C. The reaction mixture was allowed to warm to room temperature and was shaken overnight. The mixture was concentrated to dryness, and the residue was dissolved in MeOH (1 mL), passed through an ISOLUTE PSA cartridge, and washed with MeOH. The solvent was evaporated and the crude reaction product was purified using an ISOLUTE SPE-diol cartridge (DCM: 皤

MeOH 1: 1) to give the title compound (19 mg, yield 33%). NMR (DMSO + D2 0, 343 K): 4.20 (m, 1H); 3.13 (m, 2H); 3.05 (m, 1H); 2.10 (t, J = 6_2 Hz, 2H); 1.69 (m, 1H) 1.53-1 · 40 (m, 4H); 1.39-1.20 (m, 95014 -210- 200529810 14H); 0.84 (m? 9H). LC-MS 468.9, MH +. ESI POS; AQA; Spray 4kV / Defogger: 20V / Probe 250 C. Other compounds made basically according to the experimental procedure above are reported in Table E-2.

Table E-2 Example No. Structure Chemical name and analytical data E.2.1 I palpitant human γ〇Η. \ χ ° Η Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(l-one Decyl) amino] -1, ylpentyl] amino] -3-fluorenylbutyl] Η Τ ο '^ ο Analytical data: MS: MH + 468.9; 1H-NMR: (DMS0 + D20, 343 K ): 4.20 (m, 1H); 3.13 (m, 2H); 3.05 (m, 1H); 2.10 (t, J = 6.2 Hz, 2H); 1.69 (m, 1H); 1.53-1.40 (m, 4H) ; 1.39-1.20 (m, 14H); 0.84 (m, 9H). E.2.2 I pair palm human γΟΗ 0 Η 0Η \ χ ^ ΝΗ Η 〇Λ Chemical name: Dihydroxyborane, [(lR) -l -[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(octyl) amino] -1 shoulder pentyl] amino] -3-form Analytical data] MS: [M-18JH + 441.4 E.2.3 1 Pair of chemical names: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine group ( Nitroamino) fluorenyl] amino] -2-[(l-phenylcyclopentylcarbonyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] ΝηΤ Analytical data: MS : [M-18JH + 487.0 E.2.4 1 palmity (^ WH, ν ^ Nιη Η L 〇-, chemical name: dihydroxyborane, [(lR) -l-[[(2S) -5- [ [Imine (nitroamino) methyl] amino] -2-[(( 2R) -2-phenylbutylfluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 461.2 E.2.5, 丄 pair Palm 〇 -V. UM \ χ Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [[4- (l, l-Difluorenylethyl) cyclohexylcarbonyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Nh T 0′々0 Analytical data: MS: [M-18JH + 481.1 95014 -211-200529810

E.2.6 E.2.7 E.2.8 E.2.9 E.2.10 E.2.11 E.2.12 E.2.13 Palmarity

, B〆 OH

OH NH Λ

Parapetal chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (nitroamino) methyl] amino] -2-[(trans -4-pentylcyclohexylcarbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 495.4 _ Chemical Name: Dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(4-phenylbutylfluorenyl) amino]] Fluorenylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 461.4 __

Opposition

I-palm S-vAnxV〇h = H OH \ x NH Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino)) Methyl] amino] -2 _ [(4- (l, l-dimethylethyl) benzyl) amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18] H + 475.1_

Palmarity I palmarity

Parapetical chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(nonyl (Amino) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18] H + 455.1__ Chemical Name: Dihydroxyborane, [(lR) -l- [[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(2-phenphenamido) amino] small_ylpentyl] amino] -3-Methenylbutyl] Analytical data: MS: [M-18] H + 425.3 ______ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[imimine ( Nitroamino) fluorenyl] amino] -2-[(2,3-difluorobenzylidene) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data · MS: [M-18] H + 455.0_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(Dodecyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M48] H + 497.2_

Counterpart chemical name: Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2- (2 -Iodophenyl) ethenyl] amino] small ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-181H + 558.9_ 95014 • 212- 200529810

E.2.14 \ λ Palmar NH κ E.2.15 E.2.16 E.2.17 E.2.18 E.2.19 E.2.20 E.2.21 95014

• Recognize that A: H is palm 〇 \. \ χ Ν ^^ ΝΗ Η 〇Λ palm

OH

NH \ χ, Ν ^^ ΝΗ Η 〇Λ

I pair of palms C〇ynHyV ^ h t Η OH, ΝΗ Into I pair of palms ζ〇Η = H ou 0 \ χ OH • NH, owe. Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(cyclohexylcarbonyl) amino] Small_ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 425.0_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5 -[[Imine (nitroamino) methyl] amino] -2-[(2.methylbenzyl) amino] -1-onepentyl] amino] -3- 曱Analytical data: MS: [Μ-181Μ + 433.0_ Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino)) Methyl] amino] -2-[((2S) -2-phenylpropanyl) amino] -1-Wylpentyl] amino] -3-methylbutyl] Analytical data: MS: [ M-181H + 447.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] dong [(2, 2-Difluorenylbutylfluorenyl) amino] -1-_ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 413.3_ Chemical name: Dihydroxyborane, [ (lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(quinoline-2-carbonyl) amino HW pentyl] Amine] -3-Aminobutyl] Analytical data: MS: [M-181H + 470.0_ Chemical name: Hydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(non-2-enylfluorenyl) amine Yl] -1-ketopentyl] amino] -3-methylbutyl]

Two H \ X. Palmarity

NH K

， An person 『〇 丨 i H OH \, I -213- Analytical data: MS: [M-181H + 453.1_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5- [[Imine (nitroamino) methyl] amino] -2-[(2-methylcyclohexanecarbonyl) amino] -1-ketopentyl] amino] -3-methyl Butyl] Analytical data: MS: [Μ-18] Η + 439.4_ Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino ) Methyl] amino] -2-[(hept-2-enyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data MS: [M-181H + 425.4 200529810

Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2 · (3,4- Dimethylphenoxy) ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 477.3_ Chemical name: Dihydroxyboron Alkane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] · 2-[((Ι ^)-4-ethyloctyl) Amine] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 469.5_ Chemical name: Dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imino (nitroamino) fluorenyl] amino] -2-[(hexahydro-2,5-fluorenylalkylfluorenyl, Shuangwuyuan-3a (lH)- Carbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: E.2.25

Equatorial E.2.26

E.2.28 E.2.29

MS: [M-18] H + 463.5_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(Bicyclo [2.2.1] heptane-2-carbonyl) amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18 ] H + 437.4_ Chemical name: Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(5- Fluorenylhexyl) Amine HW pentyl] Amine] -3-methylbutyl] Analytical data: MS: [M-18] H + 427.0_ Chemical Name: Dihydroxyborane, [(lR)- l-[[(2S) -5-[[Imino (nitroamino) methyl] amino] -2-[(2,4-diamidino petazole-5-carbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 454.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[( 2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(furan-3-carbonyl) amino] -1-_ylpentyl] amino] -3- Fluorenylbutyl] Analytical data: MS: [M-18] H + 408.8 Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino)] 曱[Amino] amino] -2-[(2-cycloheptylethylfluorenyl) amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Data: MS: [M-18JH + 453.2 95014 -214- 200529810

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(l-methyl ring Propanecarbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 397.2_ Chemical name: Dihydroxyborane, [(lR ) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(3-methylbutylfluorenyl) amino H-ketopentyl] amine Yl] -3-fluorenylbutyl] E.2.32

Analytical data: MS: [M-18] H + 399.4_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] ] Amine] -2-[(3-phenylpropanyl) amino] -1-ketopentyl] amino] -3-methylbutyl]

Analytical data: MS: [M-18] H + 447.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] ] Amine] -2-[[((E) -3- (3-methylphenyl) propenylfluorenyl] amino] -1-ketopentyl] amino] -3-fluorenylbutyl] analysis Data: MS: [M-18] H + 459.5_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amine [Alkyl] -2-[(2-adamantane small ethanyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 491.2_ Chemistry Name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[((RS) -2- Methylbutylfluorenyl) amino H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 398.9_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(2-phenylethylfluorenyl) amino] -1-ketopentyl ] Amine] -3-methylbutyl] Analytical data: MS: [M-181H + 433.4_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (Nitroamino) methyl] amino] -2-[[2- (4-fluorenyloxy) ethenyl] amino] small ketopentyl] Amino] -3-methylbutyl] Analytical data: MS: [M-181H + 463.5 95014 -215- 200529810

E.2.38 E.2.39 E.2.40 E.2.41 E.2.42 E.2.43 E.2.44 E.2.45 95014 ^ H OH \, x, palmarity

NH o_K 0 \ x for palmity 〇-%

I palmarity = H OH palmarity

.OH 0 \ x Palmarity 〇VhyV ^ Clumsy I Palmarity 0 \, x:

X O \ 〇

NH Chemical Name: Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2- (4-Bromo Phenyl) ethenyl] amino] small_ylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M- 181H + 511.3_ Chemical name: Dihydroxyborane, [(lR ) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((RS) -4-methyloctyl) amino] -1- Ketopentyl] amino] -3_methylbutyl] Analytical data: MS: [M-18] H + 455.0_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5 -[[Imine (nitroamino) fluorenyl] amino] -2-[(2-fluoro-5-methylbenzyl) amino] small ketopentyl] amino]- 3-methylbutyl] Analytical data: MS: [M-18JH + 451.4_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine (Methyl) methyl] amino] -2-[[2- (bicyclo [2.2 · 1] hept-2-yl) ethenyl] amino] -1-ketopentyl] amino] -3- Fluorenylbutyl] Analytical data: MS: ΓΜ-18] Η + 451.0_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine (Methyl) methyl] amino] -2-[(4-phenoxybutylfluorenyl) amino] small_ylpentyl] amino] -3-methylbutyl Group] Analytical data: MS: ΓΜ-181Η + 477.4_ Chemical name: Dihydroxyboron, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] Amine] -2 · [(2-pyridylcarbonyl) amino H-fluorenylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 419.9_ Chemical Name: Dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(3-pyridylcarbonyl) amino] -1 -Ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-18] H + 420.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S ) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(tridecyl) amino H-ketopentyl] amino] -3-fluorenylbutyl ] Analytical data: MS: [M-181H + 511.6 -216- 200529810

E.2.46 E.2.47 E.2.48 E.2.49

E.2.50 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (nitroamino) methyl] amino] -2-[(8- Phenyloctyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 517.3_ Chemical name: Dihydroxyborane, [(lR) -1 -[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[4- (4-methanesulfonylphenyl) -4-ketobutylfluorenyl] Amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data MS: ΓΜ-181Η + 553.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[3- (naphthalene-2-ylthio) -propanyl] amino] -1- Ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M48] H + 529.3_ Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -5- [[Imine (nitroamino) methyl] amino] -2-[[2-[(phenylmethyl) thio] ethylfluorenyl] amino] small ketopentyl] amine] -3-Aminomethyl] Analytical data MS: [M-18JH + 479.5_ E.2.51

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(3-methylthio Propionyl) amino group> 1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 416.9_ Chemical name: Dihydroxyborane, [( lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(((2S) -1-Ethylpyridinyltetrahydropyrrole-2- (Carbonyl) amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-181H + 454.1_ E.2.52

E.2.53

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[transform-3- (2-Bromophenyl) acrylfluorenyl] amino] -1-_ylpentyl] amino] -3-methylbutyl] Analytical data MS: [M-18] H + 523.0_ Chemical name: two Hydroxyborane, [(lR) -l-[[(2S) -5-[[imino (nitroamino) fluorenyl] amino] -2-[[2- (tetrazole small group) ethyl Fluorenyl] amino] -1-ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M-181H + 425.0 95014 -217- 200529810

E.2.54 | Opposite chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [[2- (Pyrimidin-2-ylthio) ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical Data: MS: [M-18] H + 467.0 E.2.55 1 palmity \ χ HL Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amine ] -2-[[2- (4-ethylphenoxy) ethylfluorenyl] amino H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18 ] H + 476.9 E.2.56 | Parapetical chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino]] -2-[[2- (2,5-Dimethylphenyl) ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Η T Analytical data: MS : ΓΜ-18] Η + 461.4 E.2.57 丨 Palmyl chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamine)) [Amino] amino] -2-[(8-keto-8-phenyloctylmethyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] o 0 Analysis data: MS: " M-18] H + 531.0 E.2.58 | Palmarity \ χ〇Η N '^ NH H 入 化Name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2- (2- 荇Methylthio) ethoxy] amino} H-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 515.6 E.2.59 Plant. H 0, H OH \ χ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino]] 2-[[(RS) -2-Cyclopentylhexyl] amino] small ketopentyl] amino] -3-fluorenylbutyl] κ T Analytical data: MS: "M-18] H +481.1 E.2.60 | Palmarity 0 V. H 0H \ X Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -5-[[Imine (nitroamino) methyl ] Amine] -2-[[3- (4-methylphenyl) propenylfluorenyl] amino H-ketopentyl] amino] -3-fluorenylbutyl] Nh T 0_ ~. Analytical data : MS: ΓΜ-18] Η + 459.0 E.2.61 I palmity, j〇 ^ Y CHO HA Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) fluorenyl] amino] -2-[[4- (4-fluorenyloxy) -butyridinyl] amino] small ketopentyl] amino] -3-fluorenylbutyl Base] Analytical data: MS: [M-18] H + 491.6 95014 -218- 200529810

E.2.62

Opposition 掌 〇Λ Ε.2.63 E.2.64 E.2.65 E.2.66 E.2.67 ϊΎ

Ah, X, palmitic OH, VNH, palmitic chemical name: dihydroxyborane, [(lR) -l-[[(2S) -5-[[imino (nitroamino) methyl] amine [Alkyl] -2-[(2-p-phenphen-3-yl-ethynyl) amino] -1-fluorenylpentyl] amino] -3-methylbutyl] Analytical data: MS: [M -18JH + 438.9_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2 -(Dimethylamino) ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] palmity

95014 -219- Analytical data: MS: [M-18] H + 400.2_ Chemical name: Dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[Imine (nitroamino)) Methyl] amino] -2-[[5-keto-5- (thien-3-yl) pentanyl] amino] -1-ketopentyl] amino] -3-methylbutyl ] Analytical data MS: [M-181H + 494.9_ Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amine Group] -2-[(Ethyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 357.2_ Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(2-ethylthioethylamidine (Amino) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 417.4_ Chemical name: Dihydroxyborane, [(1R) -1-[[((2S &gt; 5-[[Imine (nitroamino) fluorenyl] amino] -2--2-((10-hydroxydecanoyl) amino] -1-ketopentyl] Amine] -3-Aminobutyl] Analytical data: MS: [M-2H2Q] H + 467.0_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[亚Amino (nitroamino) methyl] amino] -2-[(2-fluorenylthioethylfluorenyl) amino] small_ylpentyl] [Alkyl] -3-fluorenylbutyl] Analytical data: MS: [M-18] H + 402.9_ Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (Nitroamino) methyl] amino] -2-[[(p-phenphen-2-sulfonyl) ethenyl] amino] small ketopentyl] amino] -3-methyl Butyl] Analytical data: MS: [M-18] H + 503.1 200529810

E.2.70 E.2.71

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[3- (benzenesulfonate Fluorenyl) propanyl] amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18] H + 510.9_ Chemical Name: Dihydroxyborane, [ (lR) -l-[[((2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[(RS) -Tetrahydrofuran-3-carbonyl] amino]] small Ketopentyl] amino] -3-fluorenylbutyl] Analytical data: MS: [M481H + 413.2_ Chemical name: Dihydroxyborane, [(111) 小 [[(23) -5- |; [ Imino (nitroamino) methyl] amino] -2-[(naphthalenesulfonyl) amino] small ketopentyl] amino] -3-methylbutyl]-Analytical data: MS: [Μ48ΊΗ + 505.23_ Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [(Fluorene-2-sulfonyl) amino HW pentyl] amino] -3-methylbutyl]-Analytical data: MS: [M-181H + 505.49__ Chemical Name: Dihydroxyborane, [( lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(benzenesulfonyl) amino] -1-ketopentyl ] Amine] -3-methylbutyl]-Analytical data: MS: [M-18 1H + 455.37 Other compounds made according to the procedure described above for Example E.2 are reported in Table E-2A.

Table E-2A Example number Structural chemical name and analytical data E.2.75 1 pair of palm chemical names: ϋ Η i] f &quot; Dihydroxyborane, [(lR) -l-[[(2S) -5-[[ Imino (nitroamino) methyl] amino] -2-[[6- (ethylamido) hexyl] amino] small keto H ϋ 1 H OH pentyl] amino] 3-Methylbutyl] H Too analytical data · 0 xO MS: [M-18] H + 470.2 95014 220- 200529810

E.2.76 E.2.77 E.2.78 E.2.79 E.2.80 E.2.81

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[(RS) -2 -(4-Gaphenyl) propanyl] amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 481.1_ Chemical Name: Two Hydroxyborane, [(lR) -H [(2S) -5-[[imino (nitroamino) methyl] amino] -2-[[2- (4-benzylphenoxy) Acetyl] amino] small ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M-18JH + 524.1_ Chemical name: Dihydroxyborane, [(lR) -l- [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[3- (4-ethylphenyl) propanyl] amino] -1- Ketopentyl] amino] -3-methylbutyl] Analytical data: MS: [M48] H + 475.2_ Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -5- [[Imine (nitroamino) methyl] amino] -2- [3- [4- (heptyloxy) phenyl] -ureidoH-ketopentyl] amino] -3-methyl Butyl] Analytical data: MS: [M-18] H + 548.3_ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino ) Methyl] amino] -2-[(5-ketohexyl) amino] -1-ketopentyl] amino] -3-methylbutyl] Analytical data : MS: [M-18] H + 427.2

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[(2RS) -l -[(l, l-Difluorenylethoxy) carbonyl] hexazolium bipyridine-2-kisyl] amino] -1-steenylfluorenyl] amino] -3-methylbutyl] analysis Data: MS: [M-18] H + 526.2 Example E3 Dihydroxyborane, [(1R) -1-[[(2S, 3R) _3-hydroxy-2-[(4-butylbenzylidene) amine] Yl] small copper butyl] amino] -3-methylbutyl] 95014 221- 200529810

The 4-butylbenzamide of Example D.3.179, N-[(1S, 2R) _1-[[[(1R) -1_ [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5 , 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] -carbonyl] -2- Propyl]-(1.38 g, 2.63 mmol), 2-methylpropyldihydroxyborane (0.75 g, 7.37 mmol) and 2 N aqueous hydrochloric acid (2 ml) in methanol ( A mixture of 20 ml) and hexane (20 ml) was stirred at room temperature for 16 hours. The mixture was diluted with methanol (20 mL) and hexane (20 mL), and then the hexane layer was removed. Ethyl acetate (50 ml) was added to the methanol layer, and then it was concentrated. The residue was dissolved in ethyl acetate and the mixture was concentrated. Repeat this step (2-3 times) until an amorphous white solid is obtained. Then, the solid was triturated with diethyl ether (10-15 ml), and the supernatant was removed by decantation. Repeat this step 4 times. After trituration with additional diethyl ether (15 ml), the white solid was collected by filtration and dried under vacuum and room temperature (0.724 g, 70% yield). ^ NMRCMeOH-d ^: 7.83 (2H, d, J = 8.2); 7.34 (2H, d, J = 8.2); 4.77 (1Η, d J = 6.4); 4.36-4.28 (1H, m); 2.77 (1H , t5 J = 7.6); 2.71 (2H ?, J = ?. 6); 1 ^ 1.58 (3H, m); 1.46-L32 (4H, m); 1.29 (3H, d, J = 6.4); 〇. 97 (3H, U = 7.34); 0.94 (6H, dd, J = l_l, 6.6)

The other compounds made from -4 A π 4 枉 in accordance with the procedure described above for Example E.3 are reported in Table E-3. 95014 -222- 200529810 Table E-3

Example number Structural chemical name and analytical data E.3.1 | Counter chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(2- 荇 甲 甲) Fluorenyl) amino] -1-ketobutyl] amino] -3-fluorenylbutyl] Analytical data: NMRNMRMeOH-d ^: 8.51 (1H, s); 8.10-7.95 (4H, m); 7.66-7.58 (1H, m); 4.84 (1H, d, J = 4.1); 4.42-4.33 (1H, m); 2.77 (1H, t, J = 7.6); 1.75-1.62 (1H, m); 1.41 -1.36 (2H, m); 1.34 (3H, d, J = 6.4); 0.94 (6H, d, J = 6.5). E.3.2 Xl. 々 々〇々〇 Human Η OH Chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(p-tolyloxyacetamidamine) -1 -Ketobutyl) amino) -3 -fluorenylbutyl) Analytical data: lR NMR (MeOH-d4): 7.14 (2H, d, J = 8.5); 6.92 (2H, d, J = 8.6); 4.63-4.59 (3H, m); 4.31-4.24 (1H, m); 2.75 (1H, t, J = 7.5); 1.72-1.60 (1H, m); 1.38-1.33 (2H, m); 1.31 (3H , s); 1.17 (3H, d, J = 6.4); 0.95-0.92 (6H, m). E.3.3 1 pair of palm 〇HO # ^ Chemical name: Dihydroxyborane, [(lR) -l -[[(2S, 3R) -3-hydroxy-2-[(tridecylenyl) amino] -1-ketobutyl] amino] -3-methylbutyl] Analytical data: mp 97- 116 0C. 4 NMR (MeOH-d4): 4.55 (1H, d, J = 3.9); 4.23-4.16 (1H, m); 2.73 (1H, t, J = 7.6); 2.36-2.30 (2H, m); 1.73-1.60 (3H, m); 1.40-1.26 (20H, m); 1.22 (3H, d, J = 6.4); 0.97-0.90 (9H, m). E.3.4 I Palm OD ^ s, 〇, 〇 Human H OH Chemical Name: Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2-[(naphthalene-2-sulfonyl) amine] Yl] -1-ketobutyl] amino] -3-methylbutyl] Analytical data: NMR (MeOH-d4): 8.44 (1H, s); 8.04 (2H, d , J = 8.6); 7.98 (1H, d, J = 7.9); 7.87 (1H, d, J = 8.7); 7.71-7.61 (2H, m); 4.10-4.02 (2H, m); 2.36 (1H, dd, 1 = 6.5, 8.7); 1.40-1.26 (1H, m); 1.12 (3H, d, J = 5.9); 1.07-0.87 (2H, m); 0.74 (3H, d, J = 6.6); 0.72 (3H, d, 1 = 6.6). E.3.5 Parapetical chemical name: Dihydroxyborane, [(1trans) small [[(23,311) -3-hydroxy-2-[(4-phenylphenylhydrazone) Fluorenyl) amino] -1-ketobutyl] amino] -3-methylbutyl] Analytical data: mp 200-208 ° C. ^ NMR (MeOH-d4): 8.00 (2Η, d, J = 8.4); 7.79 (2H, d, J = 8.4); 7.70 (2H, d, J = 7.3); 7.49 (2H, t, J = 7.5); 7.41 (1H, t, J = 7.3); 4.80 ( 1H, d, J = 4.1); 4.38-4.31 (1H, m); 2.78 (1H, t, J = 7.6); 1.73-1.62 (1H, m); 1.41-1.35 (2H, m); 1.31 (3H , d, J = 6.4); 0.94 (6H, d, J = 6.5). E.3.6 I Parapalmical OH Chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) 3-Hydroxy-2-[(2,2-diamidino-decanoyl) amino] -1-ketobutyl] amino] -3-methylbutyl] Analytical data: 1U NMR (MeOH -d4): 4.40 (1H, m); 4.05-3.95 (1H, m); 1.65-1.55 (1H, m); 1.50-1.40 (2H, m); 1.25-1.15 (14H, m); 1.10 (6H , d, J = 8.8); 1.06 (3H, d, J = 6. 3); 0.82-0.88 (9H, m).

95014-223-200529810

E.3.7 Parapetal chemical name: Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2-[(4-phenoxybenzyl) amino]] -1-Ketobutyl] amino] -3-methylbutyl] Analytical data: 1K NMR (DMSO-d6 + MeOH-d4): 7.90 (2H, d, J = 8.7); 7.38 (2H, t, J = 7.9); 7.16 (1H, t, J = 7.4); 7.02 (4H, t, J = 8.6); 4.53 (1H, d, J = 4.83); 4.10-3.95 (2H, m); 2.53-2.44 (1H, m); 1.62-1.48 (1H, m); 1.22-1.49 (2H, m); 1.09 (3H, d, J = 6.35); 0.83-0.76 (6H, m). E.3.8 Palmarity A chemical name: Dihydroxyborane, [(1R) Small [[(2S, 3R) -3-hydroxy-2-[[4- (l-propoxy) butylbenzylidene] amine]] 1-ketobutyl] amino] -3-methylbutyl] Analytical data: 1U NMR (MeOH-d4): 7.88 (2H, d, J = 8.9); 7.02 (2H, d, J = 8.9) ; 4.76 (1H, d, J = 4.0); 4.32 (1H, dq, J = 4.2, 6.4); 4.03 (2H, t, J = 6.5); 2.76 (1H, t, J = 7.6); 1.89-1.79 (2H, m); 1.72-1.60 (1H, m); 1.36 (2H, t, J = 6.9); 1.28 (3H, d, J = 6.4); 1.08 (3H, t, J = 7.4); 0.93 ( 1H, dd, J = 1.8, 6.6) E.3.9 Chemical name of palmar CIH: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(3- Pyridin-3-yl-benzidine ) Amino] -1-ketobutyl] amino] -3-methylbutyl], hydrochloride analysis data: 1K NMR (MeOH-d4): 8.90 (1H, s); 8.58 (1H, d , J = 4.26); 8.22 (1H, t, J = 1.59); 8.21-8.16 (1H, m); 7.97 (1H, m); 7.93-7.89 (1H, m); 7.66 (1H, t, J = 7.78); 7.60-7.54 (1H, m); 4.80 (1H, d, J = 4.41); 4.38-4.28 (1H, m); 2.77 (1H, t, J = 7.63); 1.71-1.60 (1H, m ); 1.39-1.33 (2H, m); 1.29 (3H, d, J = 6.38); 0.95-0.90 (6H, m). E.3.10 Chemical name: Dihydroxyborane, [(lR) -l- [ [(2S, 3R) -3-Hydroxy-2-[(3-propoxy-phenylfluorenyl) amino] -1 shoulderyl] amino] -3-fluorenylbutyl] Analytical data: lH NMR (MeOH-d4): 7.49-7.44 (2H, m); 7.41 (1H, t, J = 7.82); 7.18-7.12 (1H, m); 4.76 (1H, d, J = 4.21); 4.36- 4.27 (1H, m); 4.02 (2H, t, J = 6.45); 2.77 (1H, t, J = 7.61); 1.90-1.79 (2H, m); 1.72-1.60 (1H, m); 1.40-1.34 (2H, m); 1.29 (3H, t, J = 6.39); 1.08 (3H, t, J = 7.42); 0.94 (6H, d, J = 6.48). E.3.11 1 The name of the palm chemical Hydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(3-phenylbenzyl) amino] -1-ketobutyl] amino] -3-methylbutyl] Analysis Data: lHNMR (MeOH-d4): 8.18 (1H, t, 1.7); 7.92-7.85 (2H, m); 7.73-7.69 (2H, m); 7.61 (1H, 7, J = 7.8); 7.52-7.46 (2H, m); 7.43-7.37 (1H, m); 4.81 (1H, d, J = 4.3); 4.38-4.31 (1Ή, m); 2.78 (1H, t, J = 7.6); 1.72-1.62 ( 1H, m); 1.38 (2H, t, J = 8.7); 1.31 (3H, d, J = 6.4); 0.94 (6H, d, J = 6.5).

95014 224- 200529810 E.3.12 Chemical name: CX 丄 Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2-[(4- (2-fluorophenyl) benzene Formamyl) amino] -1st-butyl] amino] each methylbutyl] Η0 ^, ^ Analytical data: lH NMR (MeOH-d4): 8.04-7.99 (2H, m); 7.75-7.69 (2H, m); 7.59-7.53 (1H, m); 7.47-7.40 (1H, m); 7.34-7.28 (1H, m); 7.28-7.20 (1H, m); 4.81 (1H, d, J = 4.2); 4.39-4.30 (1H, m); 2.79 (1H, 7.63); 1.74-1.62 (1H, m); 1.42-1.34 (2H, m); 1.32 (3H, d, J = 6.39); 0.98- 0.92 (6H, m). Example E.4 Amine] -1-Aminobutyl] Amine] -3 · methylbutyl]

In Example D.8.3, 4- (pyridine-3 · yl) benzamide, N-[(1S, 2R) small [[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexa Hydrogen-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluorenyl-2 · yl] each methylbutyl] amino] several groups]- 2-Trans-propyl]-(155 mg, 0.283 mmol), 2-fluorenylpropyldihydroxyborane (81 mg, 0.793 mmol) and 2 N aqueous hydrochloric acid (0.3 ml) in methanol (0.3 ml) 3 ml) and a heterogeneous mixture of hexane (3 ml) and stirred at room temperature for 24 hours. The hexane layer was removed and the alcoholic layer was washed with fresh hexane (about 5 ml). Ethyl acetate (10 ml) was added to the methanol layer 'and then concentrated. The residue was dissolved in ethyl acetate 'and the mixture was concentrated. Repeat this step (2J times) until an amorphous white solid is obtained. Then, the solid was triturated with ether (5 ml) and the supernatant was removed by decantation. Repeat this step. The residue (126 mg) was combined with a similarly prepared product (140 mg) and dissolved in ethyl acetate (approximately 40 ml) and oleyl alcohol (2-3 ml). The solution was a saturated solution of NaC1 (7 ml) and 95014 &gt; 225-200529810

Wash with a mixture of NaHC03 (2 ml). The layers were separated and the aqueous phase was further washed with ethyl acetate (2 X 20 mL). The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in ethyl acetate (about 20 ml) and a minimum amount of methanol, then concentrated to a small volume (about 5 ml). The white formed was collected by filtration and dried under vacuum at 50 ° C (160 mg, 65% total yield). 1H NMR (MeOH-d4): 8.90 (1H, s); 8.49 (1H, d, JN4.0); 8.20 (1H, d, J = 8.1); 8.06 (2H, d, J = 8.1 ); 7.85 (2H, d, J = 8.1); 7.58 (1H, t broad, J = 6.0); 4.80 (1H, d, J = 3.9); 4.40-4.29 (1H, m); 2.78 (1H , t, J = 7.5); 1.73-1.61 (1H, m); 1.38 (2H, t, J = 6.9); 1.31 (3H, d, J = 6.3); 0.94 (6H, d, J = 6.31 ). Other compounds made according to the procedure described above for Example E.4 are reported in Table E-4. Table E-4 Example No. Structural chemical name and analytical data-E.4.1 I Isolation of palmitate S &amp; Chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3- Hydroxy · 2-[(2-pyridylcarbonyl) aminofluoren-ketobutyl] amino] -3-fluorenylbutyl] Analytical data: lH NMR (MeOH-d4): 9.29 (1H, d, J = 1.3); 8.86 (1H, d, J = 1.3); 8.76-8.74 (1H, m); 4.75 (1H, d, J = 3.2); 4.43-4.36 (1H, m); 2.77 (1H, t, J = 7.6); 1.72-1.60 (1H, m); 1.40-1.36 (2H, m); 1.27 (3H, d, J = 7.6); 0.92 (6H, d, J = 7.6). E.4.2 1 pair Palmitic chemical name: Dihydroxyborane, [(lR) -H [(2S, 3R) -3-hydroxy-2-[(5-butyl4pyridin-2-carbonyl) amino] -1, yl Butyl] amino] -3-fluorenylbutyl] Analytical data: NMR (MeOH-d4): 8.55 (1H, s); 8.04 (1H, d, J = 7.97); 7.84 (1H, d, J = 7.96); 4.73 (1H, d, J = 2.15); 4.42-4.33 (1H, m); 2.81-2.71 (3H, m); 1.75-1.6 (3H, m); 1.5-1.3 (5H, m); 1.27 (3H, d, J = 5.64); 1.02-0.95 (3H, m); 0.94-0.89 (6H, m).

95014 -226- 200529810

Chemical name: Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(6-phenyl-azepine-2-epi) amino] amine] -1 --Butylbutyl] amino] -3-methylbutyl] Analytical data: ^ NMR (MeOH-d4): 8.20 (2H, d, J = 7.52); 8.18-8.12 (1H, m); 8.11- 8.06 (2H, m); 7.60-7.43 (3H, m); 4.77 (1H, d, J = 2.66); 4.48-4.40 (1H, m); 2.77 (1H, t, J = 7.54); 1.73-1.60 (1H, m); 1.37 (2H, d, J = 7.3); 1.31 (3H, d, J = 6.36); 0.92 (6H, d, 1 = 6.55). Example E.5 Dihydroxyborane, [( lR) -l-[[(2S) -3- (2-cropped carbonylamino) -2-[(4-butylbenzylamino) bu1-ketopropyl] amino] -3 -Methylbutyl]

Υ ΝΗ 〇% 0 makes 2-S- (4-butylbenzylamido) -3- (2-pyridylcarbonylamino) from Example D.18 [(13) -1 _ [[( 111) Small [(3,43,68,7 &amp; 11) -Hexahydro-3 \ 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxoborohydride _2-yl] each methylbutyl] aminomethyl] (120 mg '0.19 mmol, 1 equivalent) was dissolved in methanol (2 ml) and n-hexane (2 ml). In this solution, isobutyldihydroxyborane (60 mg, 0.57 mol '3 equivalents) and 4NHC1 1,4-dioxolane (0.07 ml, 0.28 mmol) have been added. 'L5 equivalent). The resulting basic mixture was stirred at room temperature for 20 hours, n-hexane was removed, the methanolic solution was washed with n-hexane ml), and evaporated under reduced pressure. The crude material was suspended in ether / n-hexane / 4 ml), stirred at / JDL, and filtered to obtain a white powder. Yield 65%, 69 mg. Analysis data: Dazzle point 145-150. 9514-227-200529810 1 H NMR (MeOD-d4): 9.3 (1H, s); 8.85 (1H, s); 8.75 (1H, s); 7.8 (2H, d); 7.3 ( 2H, d); 5 · 1 (2H, t); 4 (2H, dd); 2 · 8 (1H, t); 2.75 (2H, t); 1.65 (3H, m); 1.4 (4H, m); 1.0 (3H, t) 0.9 (6H, dd). Other compounds made according to the procedure described above for Example E.5 are reported in Table E-5. Table E-5 Example number Structural chemical name and analysis data E.5.1 0 &amp; A Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (acetamido))-2 -[(Decanoylamino)] small ketopropyl] amino] -3-methylbutyl] Analytical data: lR NMR (MeOD-d4): 4.70 (1H, d); 3.50 (2H, m ); 2.75 (1H, t); 2.25 (2H, t); 2.8 (1H, t); 1.95 (3H, s); 1.65 (3H, m); 1.35 (14H, m); 0.9 (9H, m) E.5.2. Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (propylureido) -2-[(4-butyl) -benzylamine]] Ketopropyl] amino] -3-methylbutyl] Analytical data.1K NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 4.45 (1H, br); 3.7 ( 1H, br); 3.1 (2H, t); 2.65 (2H, t); 1.7-1.2 (10H, m); 0.9 (12H, m) E.5.3 0 S: '1 / Γ Chemical name: Dihydroxyboron Alkane, [(lR) -l-[[(2S) -3- (Pananesulfonamido) · 2-[(4-butyl) -phenylamido] -1-ketopropyl]] Amine] -3-methylbutyl] Analytical data: 1K NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 3.65 (2H, m); 3.0 (3H, s); 2.8 (1H, br); 1.65 (3H, m); 1.35 (4H, m); 0.9 (12H, m). Melting point 120 ° -123 ° C E.5.4 0, OH Chemical name: Dihydroxyborane, [ (lR) -l-[[((2S) -3- [2- (lH-pyrazole) ethyl] -2-[(4-butyl) -phenylamidino] -1-ketopropyl ] Amine] -3-Aminobutyl] Analytical data: lH NMR (MeOD-d4): 7.68 (2H, d); 7.65 (1H, d); 7.43 (1H, d); 7.27 (1H, m) ; 7.24 (2H, d); 5.06 (1H, t); 4.54 (2H, m); 2.60 (2H, m); 1.5 (3H, m), 1.60-1.3 (4H, m); 0.86 (3H, t ); 0.80 (6H, d).

228-95014 200529810 E.5.5. Palmarity &quot; ShH Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (methanesulfonamido) -2--2-((4 -Butyl) -phenylphosphoniumamino] -1-ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.85 (2H, d); 7.75 ( 2H, d); Ί35-125 (4H, dd); 4.85 (1H, t); 3.9 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2.4 (3H, s), 1.65 (3H, m); 1.35 (5H, m); 1.05-0.80 (9H, m). E.5.6. Ah. \ ^ 0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-[(fluorenyloxycarbonyl, carbonylcarbonyloxyamino) -2--2-((4-butylbenzyl Fluorenylamino)] · 1-ketopropyl) amino) -3-fluorenylbutyl) Analytical data: lH NMR (MeOD-d4): 7.80 (2H, d); 7.28 (7H, m); 5.2 (2H, dd); 3.6 (2H, d); 2.8 (1H, t); 2.75 (2H, t); 1.65 (3H, m); 1.3 (4H, m); 1.0 (9H, m). Melting point 920 -96 ° CE5.7 0 ^ 〇H NH 〇ad Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -3- [〇4phen-2-ylcarbonyl) amino] -2 -[(4-Butylbenzylamido)]-1-ketopropyl] amino] -3 · methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.80 (2H, d) ; 7.7 (2H, m); 7.3 (2H, d); 7.2 (1H, t); 4.9 (2H, dd); 3.9 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 1.65 (3H, m); 1.3 (4H, m); 1.0 (3H, t) 0.9 (6H, dd). E.5.8 〇k. OH NH human chemical name: dihydroxyborane, [(lR) -l -[[(2S) -3- (Ethylamido) -2- [4-butyl-benzylamido]]-1-ketopropyl] amino] -3-amidobutyl] Analytical data: lH NMR (MeOD-d4): 7.8 (2H, d); 7.3 (2H, d); 4.8 (1H, m); 3.7 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2 (3H, s) ; 1.65 (3H, m); 1.4 (4H, m); 1.0-0.9 (3H, t), (6H, dd). Melting point 107 ° -109oC. E.5.9 I pairability οΛ0 Chemical name: Dihydroxyboron Alkane, [(lR) -l-[[(2S) -3- [〇phenphen-2-ylcarbonyl) amino]]-2-[(decylmethylamino)] small ketopropyl] amine Group] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): t 7.7 (2H, d); 7.15 (1H, t); 4.8 (1H, m); 3.7 (2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2,25 (2H, t); 1.65 (3H, m); 1.4 (14H, m); 1.0-0.9 (3H, t). E.5.10 I Paraxyl cxx ^ 々yl 〇h \ nh Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (hexamidineamino) -2-[(4-butylbenzene Fluorenylamino]] small ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.8 (2H, d); 7.3 (2H, d); 3.7 ( 2H, dd); 2.8 (1H, t); 2.75 (2H, t); 2.2 (2H, t); 1.65 (5H, m); 1.4 (9H, m); 1.0-0.9 (12H, t). 95014 -229-200529810

E.5.11 E.5.12 E.5.13 E.5.14 E.5.15 E.5.16 95014

YHnY ^ 々h ^ NH

OH

OH

-230- Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- [4-fluoro-benzenesulfonylamine] -2-[(4-butylbenzylhydrazine) Amine] Berylpropyl] Amine] -3-methylbutyl] Analytical data: lR NMR (MeOD-d4): 7.95 (2H, dd); 7.8 (2H, d); 7.3 (4H, m ); 4.8 (1H, m); 3.4 (2H, m); 2.85 (1H, t); 2.7 (2H, t); 1.7 (3H, m); 1.4 (4H, m); 1.0-0.9 (9H, t). Melting point 130 ° -132 ° C. Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- [4-fluoro-benzenesulfonamide] -2-[(dec Fluorenyl) amino] -1-ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.95 (2H, dd); 7.35 (2H, t); 4.45 (1H, t); 3.0 (2H, m); 3.4 (2H, m); 2.1 (2H, t); 1.65-1.35 (3H, m); 1.25 (14H, m); 0.85 (9H, m) .

Chemical name: Dihydroxyborane, [(1R) small [[(2S) -3- (hexanoneamino])-2-[(decanoylamino)] small ketopropyl] amino]- 3-methylbutyl] Analytical data: lU NMR (MeOD-d4): 4.45 (1H, t); 3.3 (2H, m); 2.1 (4H, tt); 1.65-1.35 (3H, m); 1.25 ( 18H, m); 0.85 (12H, m) · ___ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (hexanoneamino) -2--2-((cyclopropyl Carbonylamino)]-1-l-ketopropyl] amino] -3-methylbutyl] 3-methylbutyl] amino] carbonyl] -2- (cyclopropylcarbonylamino) ethyl]- Analytical data: lH NMR (MeOD-d4): 7.8 (2H, d); 7.2 (2H, d); 4.6 (1H, br); 3.4 (2H, m); 3.0 (2H, s); 2.7 (2H, m); 1.5 (4H, m); 1.3 (3H, m); 1.2 (4H, m); 0.9-0.6 (15H, m) ._ ^ _ Chemical name: Dihydroxyborane, [(lR) -l -[[(2S) -3-[(3,4-Dimethoxyphenyl) acetamido] -2-[(4-butylphenylamido)]-1-l-ketopropyl ] Amine] -3-methylbutyl] Analytical data: Melting point 150 ° -152 ° C lH NMR (MeOD-d4): 7.7 (2H, d); 7.2 (2H, d); 6.8 (1H, s) ; 6.75 (2H, m); 4.7 (1H, m); 3.7 (6H, m); 3.54 (2H, s); 3.35 (2H, s); 2.66 (3H, t); 1.6 (2H, t); 1.4-1.2 (2H, m); (2H, m); (2H, m); 0.9 (3H, t), 0.8 (6H, d) ._—_ Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -3- [lN-fluorenyl- 2-pyrrolylcarbonylamino] -2-[(4-butylbenzylidene) amino] -1-ketopropyl] amino] -3-fluorenylbutyl] Analytical data. LH NMR ( MeOD-d4): 7.8 (2H, d); 7.3 (2H, d); 6.9 (1H, d); 6.7 (1H, d); 6 (1H, t); 4.8 (1H, t); 3.9 (3H , s); 3.7 (2H, m); 2.7 (3H, m); 1.65 (3H, m); 1.35 (4H, m); 0.9-0.6 (9H, m). Melting point 130 ° -135oC.

200529810

E.5.17 ° HN ^ H ^ 〇々, mh2 Chemical name: Dihydroxyborane, [(lR) -1-[[(2S) -3- [4-Aminesulfonylbenzylamine] -2] -[(4-Butylbenzyl) amino] -1-ketopropyl] amino] -3-methylbutyl] Analytical data · lE NMR (MeOD-d4): 7.95 (4H, dd ); 7.8 (2H, d); 7.3 (2H, d); 4.9 (1H, t); 3.7 (2H, d); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m) 1.2 (4H, m); 0.95-0.8 (9H, m). Melting point 156 ° -159 ° CE5.18 OL 0H 'NH Chemical name: Dihydroxyborane, [(lR) -l-[[(2S)- 3- (Nicotinylamino) -2-[(4-butylbenzylamino)]-1-ketopropyl] amino] -3-methylbutyl] Analytical data: 1K NMR (MeOD-d4): 9.1 (1H, s); 8.8 (1H, d); 8.4 (1H, d); 7.8 (2H, d); 7.7 (1H, t); 7.3 (2H, d); 4.9 ( 1H, t); 3.7 (2H, m); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m); 1.4-1.2 (7H, m); 0.95-0.8 (9H, m) E.5.19 ° X 0H 0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (3-phenylureido) -2- (4-butylbenzamide] Group) Small ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 8.8 (1H, d); 7.35 (2H, d); 7.25 (2H, d) ; 7.2 (2H, t); 6.9 (1H, t); 4.7 (1H, t); 3.7-3.4 (2H, m); 2.7 (2H, t); 2.6 (1H, t); 1.6 (3H, m); 1.4-1.2 (4H, m); 0.95 -0.8 (9H, m). E.5.20 〇kNHH 〇H Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-[(4-methylsulfonyl) benzyl) Amine] -2-[(4-Butylbenzylamido)]-1-onepropyl] Amine] -3-amidinobutyl] Analytical data: lH NMR (MeOD-d4): 8.0 (4H, m); 7.8 (2H, d); 7.25 (2H, d); 4.9 (1H, br); 3.75 (2H, m); 3.2 (3H, s); 2.7 (2H, t); 2.6 ( 1H, t); 1.6 (3H, m); 1.4-1.2 (4H, m); 0.95-0.8 (9H, m). Melting point 168. -170. (: E.5.21 Palmarity 0, OH NH HNA0 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (3-phenylureido) -2- (decane Fluorenylamino) -1-ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.35 (2H, d); 7.28 (2H, dd); 7.0 (2H, t); 3.6 (2H, d); 2.75 (1H, t); 2.2 (2H, t); 1.65 (3H, m); 1.3 (14H, m); 0.9 (9H, m) E.5.22 Η 9 \ &quot; S 、 HH OH 〇Λο Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (nicotinylamidoamino) -2- (decanoylamine ) -1-ketopropyl] amino] -3-fluorenylbutyl] Analytical data lH NMR (MeOD-d4): 9.0 (1H, s); 8.8 (1H, d); 8.3 (1H, d); 7.5 (1H, t); 4.9 (1H, m); 3.9-3.6 (2H, m); 2.75 (1H, t); 2.2 (2H, t); 1.65 (3H, m); 1.3 (14H , m); 1.0-0.9 (9H, m). Melting point 136'141 ° C.

95014 -231-200529810

E.5.23 0 ^ OH HN 〇Λα Chemical name: Dihydroxyborane, [(lR) -1-[[(2R) -3- (4-methylphenylcarbonyl) -2- (decanoylamino) ) -1-ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 8.85 (2H, d); 8.0 (2H, d); 7.3 (4H, m ); 5.0 (lH, m); 3.9 (2H, m); 2.75 (3H, m); 1.65 (3H, m); 1.3 (9H, m); 0.9 (9H, m) E.5.24 1 pair of palms 0 SJ 0H N, if Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- [4- (lH-tetrazolyl) -phenylcarbonylamino]]-2- [ (4-Butylbenzylamido)]-1-l-ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 8.15 (2H, d); 7.9 (2H, d); 7.8 (2H, d); 7.3 (2H, d); 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 ( 3H, m); 1.3 (4H, m); 0.9 (9H, m). Melting point &gt; 250 ° CE5.25 Palmar ΐ, hh 0Η Μ Chemical name: Dihydroxyborane, [(lR) -l- [ [(2S) -3- (2-isoazazolylcarbonylamino) -2-[(4-butylbenzylamido)] small ketopropyl] amino] -3-methylbutyl ] Analytical data: lH NMR (MeOD-d4): 8.4 (1H, s); 7.7 (2H, d); 7.2 (2H, d); 6.9 (1H, s); 4.9 (1H, t); 3.8 (2H , m); 2. 7 (1H, t); 2.6 (2H, t); 1.5 (3H, m); 1.25 (4H, m); 0.8 (9H, m) Melting point 175Q-180 ° CE5.26 ^ Ογ ^ Η 0 Sh &quot; 6h now 〉 N \ Chemical name: Dihydroxyborane, [(1R) small [[(2S) -3- [l-methyl-1H-imidazole • 4-aminesulfonyl] -2-[(4-butyl Phenylfluorenyl) amino] small ketopropyl] amino] -3-fluorenylbutyl] Analytical data: lH NMR (MeOD-d4): 8.8 (2H, d); 8.7 (2H, s); 7.3 (2H, d); 4.9 (1H, br); 3.8 (3H, s); 3.5 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 (3H, m); 1.35 (4H, m); 0.9 (9H, m), melting point 120 ° -123 ° CE5.27 CIH 0 V OH NH kA0 Chemical name: Dihydroxyborane, [(1R) 小 [[(2S) -3- [6 -Morpholinol-pyridyl-3-pyridin-3-aminosulfonyl] -2-[(4-butylphenylfluorenyl) amino] -1-ketopropyl] amino] -3-methylbutyl Based] Hydrochloride analysis data: lH NMR (MeOD-d4): 8.35 (1H, s); 8.1 (1H, d); 7.8 (2H, d); 7.3 (3H, m); 4.9 (1H, br) ; 3.9 (4H, t); 3.8 (4H, t); 3.5 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 (3H, m); 1.35 (4H, m); 0.9 (9H, m). Melting point 182 ° -184 ° C.

95014 232- 200529810

E.5.28 rCrW '~ 乂 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (6-morpholinol nicotinamide amine) -2-[(4-but Benzamidine) amino] -1-ketopropyl) amino) -3-methylbutyl) Analytical data lR NMR (MeOD-d4): 8.5 (1H, s); 7.9 (1H, d); 7.7 (2H, d); 7.2 (2H, d); 6.7 (1H, d); 4.9 (1H, t); 3.8 (2H, ts); 3.7 (4H, d); 3.4 (4H, d) ); 2.65 (1H, t); 2.6 (2H, t); 1.60 (3H, m); 1.25 (4H, m); 0.9 (9H, m). Melting point 178Q-180 ° CE5.29 0 v. OH CIH J ° T &^; Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4- (l, 3-Difluorenyl-1H-pyrazole-5-carbonylamino) Analytical data for 2-[(4-Butylphenylamidino) amino] -1-ketopropyl) amino) -3-methylbutyl) hydrochloride: lH NMR (MeOD-d4): 7.8 (1H, d); 7.3 (2H, d); 6.65 (1H, s); 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 2.3 (3H, s); 1.60 (3H, m); 1.35 (4H, m); 0.9 (9H, m). E.5.30 to 1M · I ° ^ NH Chemical name: Dihydroxyborane, [(lR) -l-[[((2S) -3- [4-fluoro-benzenesulfonylamine]]-2-[(4-phenoxyphenylfluorenyl) amino] -1-ketopropyl] amino] -3-fluorenylbutyl] Analytical data: lH NMR (MeOD-d4): 7.95 (2H, m); 7.9 (2H, d); 7.4 (2H, m); 7.3 (2H, t); 7.25 (1H, t); 7.1 (2H, d); 7.0 (2H, d); 3.4 (2H, m); 2.8 (1H, br); 1.7 (1H, m); 1.40 (2H, m); 0.9 (6H, d). Melting point 150 ° -155 ° CE5.31 pairs Palmarity | 0,: k Chemical Name: Dihydroxyborane, [(1R) small [[(2S) -3- (4- (l, 3-Difluorenyl-1H-pyrazole-5-carbonylamino group ) -2-[(4-phenoxybenzylidene) amino] -1-ketopropyl) amino) -3-methylbutyl) carbonylamino) ethyl)-Analytical data: lH NMR (MeOD-d4): 7.9 (2H, d); 7.45 (2H, t); 7.25 (1H, t); 7.11 (2H, d); 7.05 (2H, d); 6.55 (1H, s); 5.0 (1H, t); 4.1 (3H, s); 3.9 (2H, m); 2.8 (1H, t); 2.25 (3H, s); 1.6 (1H, m); 1.35 (2H, m); 0.9 ( 6H, d) · Melting point 145 ° -148 ° CE5.32 ~. σ. 4〇 Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4-phenylureido) -2-[(4-phenoxybenzyl) amino]] -1- (ketopropyl) amino) -3-methylbutyl) Analytical data: 1U NMR (MeOD-d4): 7.9 (2H, d); 7.40 (2H, t); 7.35 (2H, d) ; 7.25 (3H, m); 7.10 (2H, d); 7.05 (3H, d); 3.75 (2H, m); 2.8 (1H, t); 1.75 (1H, m); 1.4 (2H, m); 0.9 (6H, d). Melting point 155 ° -158 ° C.

95014 233-200529810

E.5.33 JH〆〇H Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4-phenylbenzamide])-2-[(4-butylbenzene Fluorenyl) amino] -1-ketopropyl) amino) -3-methylbutyl) Analytical data: lH NMR (MeOD-d4): 7.9 (2H, d); 7.8 (2H, d) ; 7.75 (2H, d); 7.70 (2H, d); 7.45 (2H, t); 7.35 (1H, d); 7.30 (1H, d); 5.0 (1H, t); 3.95 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.65 (3H, m); 1.4 (2H, m); 1.0 (3H, t) 0.9 (6H, d) · Melting point 178 ° -180oC. E.5.34 σ ^ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4-phenylbenzylamine) -2-[(4 · phenoxybenzyl)) Amine] -1-¾ylpropyl) amino) -3-methylbutyl) Analytical data: lH NMR (MeOD-d4): 7.9 (4H, m); 7.80 (2H, d); 7.70 (2H , d); 7.4 (4H, m); 7.20 (1H, t); 7.05 (4H, d); 5.0 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 1.6 (1H, m); 1.4 (2H, m); 0.9 (6H, d) · Melting point 158 ° -160 ° CE5.35 HN- 0H. ~ Chemical Name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (phenylpropanamine) -2-[(4-butylbenzyl) amino] -1] -Aminopropyl) amino) -3-Aminobutyl) Analytical data: lH NMR (MeOD-d4): 7.85 (2H, m); 7.4 (2H, d); 7.5 (1H, d); 7.45 (2H, m); 7.35 (2H, d); 5.0 (1H, t); 3.95 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.7 (3H, m); 1.4 ( 4H, m); 1.0 (3H, t) 0.9 (9H, m). Melting point 138 ° -140 ° CE5.36 /; o ^ Palmical pCrWV ^ r ^ Η / 〇H 1 Kk Jh Chemical name: Dihydroxyboron Alkane, [(lR) -l-[[((2S) -3- (4-fluorenylbenzenesulfonyl) -ureido]> 2-[(4-butylbenzylhydrazyl) amino] -1 -Ketopropyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.85 (2H, d); 7.75 (2H, d); 7.3 (2H, d); 7.25 (2H, d); 4.7 (1H, t); 3.65 (2H, m); 2.75 (1H, t); 2.7 (2H, t); 1.7 (3H, m); 1.4 (4H, m); 1.0- 0.9 (9H, m). Melting point 175 ° -1770C. E.5.37 [/ OH HN Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4- (2- ( 4-pyridyl) -1,3-, sedazole-4-carbonylamino))-2-[(4-butylphenylfluorenyl) amino H-ketopropyl) amino) -3- Analytical data lH NMR (MeOD-d4): 8.7 (2H, d); 8.45 (lH, s); 8.05 (2H, d) 7.8 (2H, d); 7.3 (2H, d); 5.05 (1H, t); 4.0 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.7 (3H, m); 1.4 (4H, m); 0.9 (3H, t); 0.8 (6H, dd). Melting point 155 ° -158 ° C.

95014 234- 200529810

E.5.38 ^ 〇H 丨 palladium 0 〇Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (l-methanesulfonylhexahydropyridine-4-carbonyl Amino group) -2-[(4-Butylbenzylamido)] small ketopropyl] amino] -3-methylbutyl] Analytical data: 1K NMR (MeOD-d4): 9.9 (1H , br); 8.35 (1H, t); 7.8 (2H, d); 7.3 (2H, d); 4.9 (1H, t); 3.7 (4H, m); 2.8 (3H, s); 2.75 (4H, m); 2.3 (1H, m); 1.85-1.6 (7H, m); 1.3 (4H, m) 0.9 (9H, m); melting point 170 ° -173 ° CE5.39 〇L 〇η ^ ΝΗ Chemical name: two Hydroxyborane, [(lR) -l-[[(2S) -3-[(2-fluorenyl) sulfonylamino]]-2-[(4-butylphenylhydrazine)] ketone Propyl] amino] -3-methylbutyl] Analytical data: lH NMR (MeOD-d4): 7.95 (1H, dd); 7.8 (2H, d); 7.58 (1H, dd); 7.32 (2H , d); 7.18 (1H, dd); 4.8 (1H, m); 3.23 (2H, m); 2.66 (1H, t); 1.3-1.23 (8H, m); 0.9 (3H, t), 0.8 ( 6H, d). E.5.40 0, ΟΗ ΝΗ Chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3- (4- (lH-1, 2,4-triazole small Group) Aniline)]-2-[(4-Butylphenylamidino) amino] -1-ketopropyl] amino] -3-methylbutyl] hydrochloride analysis data lR NMR (MeOD-d4): 9.8 (1H, s); 8.6 (1H, s); 8.08 (2H, d); 8.01 (2H, d); 7.8 (2H, d); 7.3 (2H, d); 5.05 (1H, t); 3.9 (2H, m); 2.8 (1H, t); 2.7 (2H, t); 1.6 (3H, m); 1.3 (4H, m); 1.0 (3H, t); 0.9 (6H, dd). Melting point 192 ° -195 ° CE5.41 〇y 〇Η ΝΝ Chemical name: dihydroxyborane, [(lR) -1-[[(2R) -3- (4-fluorenylphenylcarbonyl ) -2- (decanoylamino) -1-ketopropyl] amino] -3-fluorenylbutyl] Analytical data: lH NMR (MeOD-d4): 7.85 (2H, d); 7.8 ( 2H, d); 7.35 (4H, m); 5 (1H, m); 4.05 (1H, m); 3.95 (1H, m); 2.75 (2H, t); 1.65 (2H, m); 1.35 (10H , m): 1.0 (3H, t), 0.85 (6H, d). E.5.42 1 palmarity 0 L OH X HN \ 〇ό Chemical name: dihydroxyborane, [(lR) -l-[[ (2S) -3- (4-phenylureido) -2- (decanoylaminoM-ketopropyl) amino) -3-methylbutyl) E.5.43. , HL human chemical name: Dihydroxyborane, [(lR) -l-[[(2S) -3-Ethylamido-2-decylamido-1-stearylpropyl] amino]- 3-methylbutyl]

95014 -235. 200529810 Example F.l

Decylamine, N _ [(1S) _1 _ [[[(1R) Small [(4R, 5R) _4,5-dicyclohexyl ^, cut oxygen oxo-2-yl] _3_methylbutyl] Amine] several groups] _4_ [丨 imino (nitroamino) methyl] amino group] butyl]-

In the dihydroxyborane obtained as in Example E.2, [[Imine (songylamino) methyl] amino] -2-[(decylamino) amino] -1-one-pentyl [Amino] amino] -3-methylbutyl]-(125 mg, 0.26 mmol) in a suspension of a mixture of ether (0.5 ml) and dichloromethane (1 ml), a few drops of methanol were added Until the solid is completely dissolved. (1R, 2R) -1,2-dicyclohexyl-1,2-ethanediol (61 mg, 0.26 mmol) was added, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated to dryness and the residue was purified by column chromatography (silica gel) and dissolved in a 50:50 ethyl acetate: hexane mixture. The product was then triturated with hexane and the solvent was removed by decantation. The development was repeated two more times. The product was obtained as a soil-like solid (65 mg, 37% yield). 75-100 ° C · ^ NMRCDMSO-d ^: 8.99 (1H, d5 J = 2.5 Hz); 8.52 (lH, br); 7.98 (1H5 d5 J = 8.05); 7.88 (2H5 br); 3.48 (2¾ d , J = 5.7); 3.14 (2H5 m); 2.55 (1H, m); 2.19 (lH, m); 2_10 (2H, m); 1.79 (2H, m); 1.74-1.35 (16H, m); 1 24 (22H, m); 1.12 (5H, m); 0.89 (4H, m); 0.84 (9H, m). 95014 -236-200529810 Example F.2 4-Phenylbutylamidine, N _ [(1S ) _1 _ [[[((1R) _1_ [13,15_dioxo-14-borobisspiro [5 · 0 · 5 · 3] _fifteen_14_yl] -3_methylbutyl] amino] Kis] winter [[imino (sonylamino) methyl] · amino 1 butyl l ·

The title compound was prepared according to the procedure described above for Example F.1, using an appropriate dihydroxyborane starting material and dicyclohexyl-1, Γ-diol. Analysis results: 1H NMR (DMSO-d6): 8.79 (1Η, d, J = 2.5 Ηζ); 8.52 (1Η, br); 8.00 (1H, d, J = 7.94); 7.85 (2H, br); 7.31-7.23 (2H, m); 7.20-7.14 (3H, m); 4.40-4.30 (1H, m); 3.15 (2H? M); 2.55 (3H, m); 2.14 (2H , t? J = 7.3 Hz); 1.78 (2H, q, J = 7.3 Hz); 1.70-0.97 (27H, m); 0.84 (3H, t, J = 6.7 Hz); 0.83 (3H, t, J = 6.7 Hz). Example F.2.1 4-Butylbenzamide, N _ [(1S, 2R) -1-[[[((1R) _1- [13,15-dioxo-14-borobisspiro [5 · 0.5 · 3] Pentadec-14-yl] -3 · methylbutyl] amino] carbonyl] -2-hydroxypropyl]-

The title compound was prepared according to the procedure described above for Example F.1, using an appropriate dihydroxyborane starting material and dicyclohexyl-1, Γ-diol. 95014 -237- 200529810 Analysis results · WNMRpMSOcU: 8.98 (lH, sbr.); 8.00 (lH, d, J =: 8.5); 7.81 (2H, d, J = 8.2); 7.31 (2H, d, J = 8.2); 5.03 (1H, d, J = 6.2); 4.49 (1H, dd, J = 8.5, 5.0); 4.07-3.98 (1H, m); 2.64 (1H, t, J = 7.6); 2.57-2.50 (1H, m); 1.65-1.21 (21H, m); 1.14-1 · 00 (9H, m); 0.90 (3H, t, J = 7.4); 0.85 (6H , D, 6.5). Example Gl

10- (1,3-diketo-1,3_dihydro-isofluorin-2-yl) -decanoic acid 1,3-Dihydroisoglyoxol comes from 10_H dilute alcohol (4.23 g, 24.8 mmol), phthalimide (3.65 g, 24.8 mmol) and triphenylphosphine ( 6.51 g, 24.8 mmol) in a mixture of anhydrous tetrahydrofuran (30 ml), slowly add a solution of DEAD (3.9 ml, 24.8 mmol) in anhydrous tetrahydrofuran (10 ml) , While keeping the temperature below 8-10 ° C. After 2 hours, additional DEAD (1.0 mL, • 6.37 mmol) and triphenylphosphine (1.3 g, 4.96 mmol) were added, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and the residue was triturated with ethyl acetate (50 ml). The solids were removed by filtration and the bars were washed with ether (2 X 50 mL). The combined filtrates were concentrated, and the residue was triturated with hexane (50 ml) at 40 ° C. The solid formed was removed by filtration and washed with hexane (2 X 50 mL). The combined filtrates were concentrated and the residue was purified by column chromatography and dissolved in a 10: 2 hexane: ethyl acetate mixture. The product was obtained as a low point white solid (4.9 g, 66% yield).

25-30 ° C 95014 -238-200529810 1HNMR (DMSO-d6) 7.83 (4H, m); 5.76 (lH, m); 4.96 (1H, dq? J = 17.2, 1.6 Hz); 4.90 (1H, ddt , J = 1.0.2, 2.2, U); 3.54 (2H, t, J = 7.1), 1.97 (2H, q, J = 6.7); 1.56 (2H, m); 1.35-1.15 (14H, m). Step 2: 10- (1,3-diketo-I) dihydroisofluorinyl) decanoic acid

Place 2-undec-10-enyl_ι, 3_diketo-i, 3-dihydroisoindole (2 g, 6.68 mmol) with Aliquat® 336 (0.2 g) in step 1 A solution of alkane (20 ml) and acetic acid (6 ml) was added dropwise to a solution of potassium permanganate (2.76 g, 20 mmol) in water (28 ml), at the same time. Cool at ° C. The reaction mixture was stirred at room temperature for 7 hours, and then an aqueous sodium hydrogen sulfite solution was added until the purple color disappeared. The mixture was then extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography 'to dissolve the mixture in 2: 1 hexane: ethyl acetate. The product was obtained as a white solid (1-29 g, 61% yield).

58-60 ° C 1H NMR (DMSO-d6) 11 · 95 (1H, br); 7.85 (4H, m); 3.55 (2H, t, J = 7.2 Hz); 2.17 (2H, t , J = 7.2 Hz); 1.7-1.4 (4H, m); 1.22 (10H, m). Example G.2 6- (phenylphenylamino) hexanoic acid is used to regenerate benzene chloride (2.5 ml, 19 mmol) Mol) was added to a solution of 6-aminohexanoic acid (1 g, 7.62 mmol) in 2NNaOH (22 ml) and dioxin (3 ml), at 0 ° C -5 ° C. Stir. The mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was washed with ethyl acetate (50 ml), then acidified to pH 2 with 37% hydrochloric acid, and extracted with ethyl acetate (2 x 50 ml). The combined organic layers were dehydrated with sodium sulfate and reduced. The residue was triturated with hexanes 95014-239-200529810. The solid was collected by filtration and dried under vacuum at 50 ° C to provide 1-1 g of the title compound (55% yield).

Melting point 113-115 ° C ^ NMRCDMSO- ^): 11.96 (1H5s); 7.79 (2H5m); 7.60 (4H5 m); 2.71 (2H, m); 2.13 (2H, t, J = 7.14 Hz); 1.38 (4H, m); 1.21 (2H, m). Example G.3 6- (Ethylsulfonylamino) hexanoate will vaporize ethanesulfonium (3.9 ml, 41.1 mmol) in dioxane The solution in Lupin (10 ml) was added to a solution of 6-aminohexanoic acid (2 g, 15.2 mmol) in NaOH (56 ml) and dioxolane (10 ml), Simultaneously incubate at -5C. The pH of the reaction mixture was adjusted to 8-9 by adding a 25% sodium hydroxide solution. The mixture was allowed to warm to room temperature and stirred for 30 minutes. Add another 25% NaOH solution to adjust the pH to about u. After 35 hours, 1N hydrochloric acid (15 ml) and ethyl acetate (60 ml) were added. The organic layer was dried over sodium sulfate and concentrated. The residue was triturated with a mixture of ethyl acetate (5 mL) and hexane (μ # mL). The solid was collected by filtration and dried to provide u g of the title compound (40% yield). ^ NMRCDMSO- ^): 11.9 (1H5s); 6.97 (lH, t5 J = 5.7 Hz); 2.97 (2H5 q5 J = 7.1); 2.88 (2H, q, J = 6.6); 2.2 (2H, t, J = 7.3); 1.47 (4H, m); 1.29 (2H, m); U8 (3H, t, J = 7.3) · Example G.4 8_ (ethoxyamido) octyl

Bathe of vaporized ethanesulfonium (1.5 ml, 15-7 mmol) in dioxolane (5 ml), added to 8-aminocaprylic acid (1 g, 6.28 mmol) at 1N 95014 -240- 200529810

In a solution of NaOH (22 ml) and dioxin (5 ml), at the same time, stir at 0 ° C-5 ° C. The mixture was allowed to warm to room temperature and stirred for 3.5 minutes. During this period, the pH was adjusted to 7-8 by adding 25% NaOH solution at 1 hour intervals. The reaction mixture was washed with diethyl ether (30 ml). The pH was adjusted to 1-2 by adding IN HC1, and the mixture was extracted with ethyl acetate (70 ml). The organic layer was dried over sodium sulfate and concentrated. The residue was triturated with a mixture of ether. The solid was collected by filtration and dried under vacuum to obtain 600 mg of the title compound (38% yield). ^ NMRCDMSO-de): 11.9 (lH, s); 6.96 (1H, t? J = 6 Hz); 2.96 (2H5qJ = 7.1), 2.88 (2H, q, J = 6.6); 2.2 (2H, t, J = 7.3); 1.45 (4H, m); 1.26 (6H, m); 1.18 (3H, t, J = 7.3). Example G.5 3-amino-2-S-[(l, l-dimethylformate Ethoxycarbonyl) amino]] benzyl propionate

Step 1: N-Third-butoxycarbonyl-L-aspartin [commercially available]

L-aspartin (15 g, 0.113 mol, 1 eq.) And sodium carbonate (12 g '0.113 mol) were dissolved in water (225 ml) and ι, 4-dioxolane ( 225 ml). To this solution, di-tertiary-butyl dicarbonate (30 g, 0137 mol, 1.2 equivalents) was added, and the mixture was stirred overnight. The solvent was evaporated under reduced pressure until 1,4-dioxolane was distilled off, and the pH was adjusted to 2 with HC1 37% to obtain a white solid, which was filtered, washed with water, and dried. 95014 -241-200529810 91% yield. 24 grams. Analytical data: melting point 175 ° C -180 ° C (literature 175 °. 1H NMR (DMSO-d6) 12.5 (1H, br); 7.31 (lH, br); 6.91 (lH, bf); 6.87 (1H, d , J = 8.4 Hz); 4 · 23 (1H, q, J = 7.7 Hz); 2.56-2.36 (2H, m); 1.38 (9H, s). Step 2 ·· N-[(l, l- 二Methylethoxycarbonyl) amino] -L-aspartic acid benzyl ester 0 The compound was prepared according to Bioorg. Med. Chem "6 (1998) 1185-1208. The N-[(l, l- Dimethylethoxycarbonyl) amino] aspartin (20.7 g, 89 mM, 1 equivalent) was dissolved in methanol (500 ml), and carbonic acid shavings (15.97 g, 49 mM) were added , 0.55 equivalent). The solvent was evaporated to obtain a white solid, which was dissolved in N, N-dimethylformamide (200 ml). To this suspension, benzyl bromide was added dropwise ( 11.6 ml, 98 mmol, 1.1 equivalents), and the mixture was stirred overnight. The solvent was reduced under reduced pressure, water (300 ml) was added, and the mixture was extracted with ethyl acetate (200 ml), It was washed with brine (50 ml) and the solvent was removed under reduced pressure to obtain a crude product, which was suspended in a normal solution. Hexane (160 liters), filtered, and dried under vacuum to give 14.68 g of a white solid. Yield 51%. Analytical data: melting point 113.-115. (:. 1HNMR (DMSO-d6) 7.35 (6H? M); 7.13 (1H? D, J = 7.9 Hz); 6.94 (1H, br s); 5.10 (2H, s); 4.39 (1H, q, J = 7.4 Hz); 2.6-2.4 (2H, m); 2.03 (2H, ^^ 7.3); 1.37 (9H3s). Step 3: 3-amino-2-S-[(l, l-dimethylethoxycarbonyl) amino p Benzyl propionate 95014 -242 · 200529810 ο Make N-[(1,1-dimethylethoxycarbonyl) amino PL-aspartame fluorenyl ester (2 g, 6.3 mmol, 1 (Equivalent) was dissolved in acetonitrile (80 mL) and water (80 mL). The solution was cooled to 0-5 ° C, and Ephenyldiacetate (3 g, 9.3 mmol, 1.5 equivalents) was added in portions. The mixture was stirred at 0 ° C for 30 minutes, and then at room temperature for 4 hours. The organic solvent was removed under vacuum, diethyl ether and HC11N were added. The liquid layer was separated, and methane (100 mL) and Extraction with sodium bicarbonate (3.5 g). The organic solvent was dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain 0.65 g of a colorless oil. Yield 36% Analytical data: 1H NMR (DMSO-d6) 7.45-7.20 (7Η, m); 7.20 (1H, d5 J = 7.7 Hz); 5.13 (2¾ AB q, J = 12.8); 4.01 (1H, m ); 2.80 (2H, m); 1.38 (9H, s). Example G.6 (2S) -2-[(l, l-,-methylethoxymethylene) amino] _3 _ [(4 -Methylbenzyl) amino j propionic acid

Step 1 · 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (4-methylbenzylamino) propyl propionate

〇 95014 -243-200529810

Soluble 3-amino-2-S _ [(l, l-dimethylethoxycarbonyl) amino p-propionate (690 mg, 2.34 mmol, 1 equivalent) of Example G.5 To anhydrous dmf (20 ml) and add TBTU (900 mg, 2.98 mmol, ι · 2 equivalent). The mixture was stirred at room temperature for 10 minutes, cooled to 0-5 ° C in an ice bath, and NMM (0.51 ml, 4.68 mmol, 2 equivalents) and 4-fluorenylbenzoic acid (38 mg , 2.81 millimoles, 1.2 equivalents). The mixture was stirred at room temperature for 3 hours, poured into water (100 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed with 2% (50 ml) of citric acid solution, 2% (50 ml) of sodium bicarbonate, 2% (50 ml) of NaCl, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain 1 Grams of oil. Yield was quantified. Analytical data: 1H NMR (DMSO-d6) 8.46 (1H5 br t5 J = 5.7 Hz); 7.70 (2H, d? J = 8.0); 7.35- 7 · 2 (8H, m); 5.07 (2H, s); 4 · 29 (1H, m); 3.67 (1H, m); 3.58 (1H, m); 2.36 (3H, s); 1.37 (9H, s). Step 2 ·· (2S) -2- [ (l, l-Difluorenylethoxycarbonyl) amino] (4-methylbenzylamino) propionic acid

Make 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (4-methylbenzylamino) -benzyl propionate (930 mg, 2.25 mmol) from step 1 Mol) was dissolved in methanol (25 ml) and Pd / C 10% (90 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. Pd / C was filtered, and the solution was evaporated under reduced pressure to obtain 650 mmol 95014-244-200529810 g of white foam. The yield was 86%. Analytical data: 1H NMR (DMSO-d6): 12.5 (1H, br); 8.40 (1H513 J = 5.7 Hz); 7.71 (2H, d? J = 8.05 Hz); 7.27 (2H? D? J = 8.05 Hz) ; 7.09 (1H5 d5 J = 7.9); 4.17 (1H, m); 3.57 (2H, m); 2.35 (3H, s); 1.37 (9H, m) · Example G.7 2-S_ [ (l, l-dimethylethoxycarbonyl) amino] -3- (hexamidineamino) propionic acid

0 Step 1: 2 each [(1,1-dimethylethoxycarbonyl) amino] each (hexamethylamino) benzyl propionate

Hexanoic acid (450 耄 g '3.87 耄 mol, 2 · eq) was dissolved in anhydrous DMF (15ml) and TBTU (1.24g, 3.87mmol, 1.2eq) was added, and the mixture was at room temperature Stir for 20 minutes and then cool to 0-5 ° C in an ice bath. Example G.5, 3-Amino-2 each [(1,1-dimethylethoxycarbonyl) amino] propyl propionate (950 mg, 3.22 mmol, 1 equivalent) and NMM (丨0.06 ml, 9 61 millimoles, 2.5 equivalents). The mixture was stirred at room temperature overnight, poured into water (150 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with 2% (50 ml) of citric acid solution, 2% (50 ml) of sodium bicarbonate, and 0.2% (50 ml) of sodium bicarbonate, dried with anhydrous sulfuric acid to dry anhydrous, and evaporated under reduced pressure. The crude product was obtained and purified by column chromatography (eluent: n-hexane / acetic acid 95014-245 · 200529810 ethyl ester 2/1, Rf = 0.52) 0.5 g of colorless oil. The yield is 40%. Analytical data: ^ NMR (DMSO-d6). Δκ: 7.87 (1H? Br t? J = 6.2 Hz); 7.35 (5H, m); 7.14 (1H5 d? J-8.2); 5.07 (2H, s); 4.14 (lH, m); 3.37 (2H, m); 2.00 (2H, t, J = 7.1); 1.43 (2H, m); 1.36 (9H, s); 1.3-1.1 (4H, m); 0.83 ( 3H, t, J = 7.1 Hz) Step 2 · 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (hexamidineamino) propionic acid

Dissolve 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (hexamethylamino) propanoic acid propionate (500 mg, 1.27 mmol) in Step 1 Methanol (15 ml) and 10% Pd / C (50 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. Pd / C was filtered, and the solution was evaporated under reduced pressure to obtain 300 mg of a white solid. Yield: 78%. Analytical data: melting point 123-125 ° C.

^ NMR (DMSO-d6) .: 12.6 (1H3 br); 7.84 (1H, br t); 6.87 (1H, d5 J = 7.5 Hz); 4.00 (1H, m); 3.32 (2H, m); 2.04 ( 2H, t, J = 7.5); 1.47 (2H, m); 1.38 (9H, s); 1.3-1.1 (4H, m); 0.85 (3H, t, J = 7.1Hz) Example G.8 2-S -Second-butoxyamino group_3- (4-amino group amino group) propionic acid 95014 -246- 200529810 γγ 'ο

Step 1: 2-S-[(l'l-dimethylethoxyM) amino group] _3_ (4-amino group amino group) propionate

Soluble 3-amino-2-S-[(1,1-dimethylethoxycarbonyl) amino] propanoic acid S (1.25 g, 4.24 mmol, 1 equivalent) in Example G.5 In anhydrous digas methane (20 ml), and let the valley liquid cool to 0-5 C under gas. Add TEA (0.65 ml, 4.67 mmol, U equivalent) and anhydrous 4-fluoro-continuum (0.9 g, 4.67 mmol, 1.1 equivalent) in anhydrous digas methane (10 ml). ). The mixture was stirred at room temperature for 1 hour, evaporated under reduced pressure, and ether (25 ml) was added, and a white solid was obtained, which was filtered and dried under vacuum to give L89 g of product. Yield: 99%. Analytical data: melting point 105-107 ° C · TLC silicone (eluent: n-hexane / ethyl acetate 1/1, Rf = 0.55). ^ NMR (DMSO-d6). ΔΗ: 7.91 (1Η, t5 J = 6.2 Hz); 7.85 (2H5 dd5 J = 5.3? 8.8); 7.43 (2H515 J = 8.8); 7.35 (5H, m); 7.15 (lH, d, J = 8.2); 5.09 (2H, s); 4.14 ( lH, m); 3.10 (2H, m); 1.36 (9H5s). Step 2: 2-S-[(l, l-dimethylethoxycarbonyl) amino] -3- (4-fluorosulfofluorene Aminoamino) 95014 -247- 200529810 propionic acid

2-S-[(l, l-Difluorenylethoxycarbonyl) amino] -3- (4-fluorosulfofluorenylamino) propionate (1.8 g, 3.98) Millimolar) was dissolved in methanol (30 ml) and Pd / C 10% (180 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. Pd / C was filtered, and the solution was evaporated under reduced pressure to obtain 1.39 g of a colorless oil. Yield 97%. Analytical data. ^ NMR (DMSO-d6). Known: 12_7 (lH, br); 7.83 (2Η, dd, J = 5.3, 8.8); 7.78 (lH, brt, J = 5.5); 7.42 ( 2H, t5 J = 8.8); 6.87 (1H, d5 J = 8.6); 3.99 (1H, m); 3.03 (2H? M); 1.36 (9H, s). Example G.9 2-S _ [(l, l · dimethylethoxycarbonyl) amino group] _3- (3,4_dimethoxyphenylacetamido) -propionic acid

Step 1: 2-S-[(l, l-dimethylethoxycarbonyl) amino group] _3_ (3 4_dimethoxyphenylacetamido) -propionate group 95014 -248- 200529810

Dissolve 3,4-dimethoxy-phenylacetic acid (720 mg, 3.66 mmol, 2 equivalents) in anhydrous DMF (20 ml) and add TBTU (1.17 g, 3.66 mmol) , L2 equivalent), the mixture was stirred at room temperature for 20 minutes, and then cooled to 0-5 ° C in an ice bath. Example G.5 3-Amino-2-S-tertiary-butoxychitylamino-propionic acid benzyl ester (0.9 g, 3.05 mmol, 1 equivalent) and (10 ml, 9.15 mmol Mohr, 2.5 equivalents). The mixture was stirred at 0 ° C for 2 hours, then poured into water (200 ml) and extracted with ethyl acetate (100 ml). The organic layer was washed with a solution: 2% citric acid (20 ml), 2% sodium bicarbonate (20 ml), 2% NaCl (20 ml), dried over anhydrous sodium sulfate, and evaporated under reduced pressure, and The crude product was obtained and purified by silica gel chromatography (eluent: n-hexane / ethyl acetate 1/1, Rf = 0.57) to obtain 1 g of a colorless oil. Yield 69

Analytical data: WNMIUDMSO-cU cJH: 8.02 (lH, t, J = 5.7Hz); 7.34 (5Η, m); 7.17 (lH, d, J = 7.7); 6.82 (2H, m); 6.71 (lH , Dd, J = 1.5, 8.2); 5.03 (2Η, s); 4.14 (lH, m); 3.71 (3H, s); 3.69 (3H, s); 3.39 (2H, m); 1.36 (9H S) Step 2 24-[(1,1-dimethylethoxycarbonyl) amino] -3- (3,4-dimethoxyphenylacetamido) -propionic acid 95014- 249-200529810

Make 2-S-[(l, l-dimethylethoxyquinyl) amino] -3- (3,4-dimethoxyphenylacetamido) -propionic acid, benzyl in step 1 The ester (1 g, 2.1 mmol) was dissolved in methanol (30 ml) and Pd / C 10% (10 mg) was added. The mixture was hydrogenated at atmospheric pressure for 1 hour. Pd / C was filtered, and the solution was evaporated under reduced pressure to obtain 0.73 g of a white foam. The yield was 91%. Analytical data: iHNMRpMSO-cy. ^ H: 12.7 (lH, br); 8.06 (lH, t, J = 5.9 Hz); 7.00 (1H, d, J = 8.05); 6.91 (2H, m); 6.80 (1H, dd, J = 1.5, 8 · 4); 4.08 (1H, m); 3.80 (3H5 s); 3.78 (3H, s); 3.5-3.3 (2H, m); 1.36 (9H, s). Example G.10 2-[(l, l-dimethylethoxycarbonyl) amino] -3- (3-phenylureido) propionic acid

Step 1: 2-[(1,1-Dimethylethoxycarbonyl) amino] winter (3-phenylureido) propionate

At room temperature, the 3-amino-di-difluorenylethoxycarbonyl) amino] benzyl propionate (1.14 g, 3.87 mmol, 1 equivalent) of Example G 5 was dissolved in dichloromethane (2 〇 strokes). The solution was cooled to 0-5. 〇, and phenyl isocyanate (0.42 ml, 3.87 mmol, 1 equivalent) in methane (5 95014-250-200529810 ml) was added dropwise. The solution was stirred at room temperature for 1 hour, evaporated under reduced pressure, and purified by silica gel chromatography (eluent n-hexane / ethyl acetate 1/1) to obtain 0.71 g of a glassy solid, which was suspended in ether. Medium to give a white solid. Yield 44%. Analytical data · TLC stone gum (solvent n-hexane / ethyl acetate g 1/1, R.f. = 0.44), melting point 48-50 ° C. iHNMRpMSO-dd. 5h: 8.68 (lH, s); 7.4-7.27 (8H, m); 7.22 (2H, t, J = 8.2 Hz); 6.90 (1H, t, J = 7.3); 6.26 (1H, t , J = 5.7); 5.11 (2H, s); 4.12 (1H, m); 3.58 (1H, m); 3.28 (1H, m); 1.38 (9H, s) · Step 2: 2-[( l, l-dimethylethoxycarbonyl) amino] -3- (3-phenylureido) propionic acid

Make 2-S-[(l, l-difluorenylethoxycarbonyl) amino] -3- (3-phenylureido) propionate in step 1 (0.7 g, 1.7 mmol) Dissolved in methanol (25 ml) and added 10% Pd / C (70 mg). The mixture was hydrogenated at atmospheric pressure for 1 hour. Pd / C was filtered, and the solution was evaporated under reduced pressure to obtain 0.47 g of the desired product. The yield is 87%. Analytical data iHNMRpMSO-dJ.SH: 12.6 (lH, bio; 8.66 (lH, s); 7.37 (2H, d, J = 8.1 Hz); 7.21 (2H, t, J = 7.50); 7.08 (lH , D, J = 7.9); 6.89 (1H, t, J = 7.3); 6.21 (lH, t, J = 5_9); 3.98 (lH, m); 3.54 (lH, m); 3.22 (lH, m) 1.38 (9H, s). Example G.ll 95014 • 251-200529810 Synthesis of other compounds The following compounds can be exemplified by the methods described in steps 1 and 2 of G.6-G.10, from Example G.5-3 -Amino-2-S-[(l, l-dimethylethoxycarbonyl) amino] propanoic acid y-ester was prepared. G.11.1 2-[(1,1-dimethylethoxy Carbonyl) amino] -3_ (acetamido) propionic acid &gt; ΓΥΗνυ ^ 〇η VNH 〇 human G.11.2 2-[(1,1-dimethylethoxycarbonyl) amino] each (9-th Methyloxyamine formamyl)) propanoic acid 0 S3 G.11.3 2-IX1,1-dimethylethoxycarbonyl) amino] -3- (3-pentylureido) propionic acid YvsAh 1 0 G .11.4 2-[(1,1-Dimethylethoxycarbonyl) amino] -3- (methanesulfonylamino) propionic acid ^ NΗ 0 = S = 〇1 G.11.5 2-[(U-dimethyl Ethoxycarbonyl) amino group] _3 _ [(ethoxycarbonylsuccinyl) -amidino] ethyl] -propionic acid_decavA 0 7. —F 0 Example G.12 2-[(1,1-Dimethylethoxycarbonyl) amino] Each (3-narrowoxycarbonylamino) propionic acid

(TΛ step 1: Ν2- (third-butoxycarbonyl) -L-2,3-diaminopropionic acid

95014 -252- 200529810 Suspend N-third oxycarbonyl aspartate (8 g, Moore, 1 equivalent) from Example G · 5 step 1 or commercially available in ethyl acetate (72 ml), Acetonitrile (72 mL) and water (36 mL) were added at 5 ° C, iodobenzenediacetate (13.3 g '0.041 mole, 1.2 equivalents). The mixture was stirred at IO-25 ° C for 3-4 hours, whereupon a white solid appeared. The solid was filtered, washed with diethyl ether, and dried under vacuum to give a white powder. Yield 57%. 4 g. Analytical data: melting point 210 ° C -211 ° C · Silicone (digas methane / methanol / fluorene acetate 5/3/1) Rf0.5.1HNMR (DMSO-d6) 4.15 (lH, t); 3.15 (2H, m) ; 1.45 (9H, s); Step 2: 2-[(l, l-dimethylethoxyquinyl) amino] aspartyloxycarbonylamino) propionic acid

° VNH 〇A at 25 ° C, so that the N2- (third-butoxycarbonyl) core 2,3-diaminopropionic acid (3.8 g, 0.018 mol, 1 equivalent) from Step 1 was dissolved in sodium carbonate Aqueous solution 10% (2 2 equivalents) in 1,4-dioxolane (38 ml). To this solution, chloro # formate (3 ml, 0.020 mol, U equivalent) was added dropwise, and the solution was stirred at 25 ° C for 3 hours. When the reaction was complete, the mixture was poured into water (100 ml) and washed with ether (100 ml). To the aqueous solution was added HC137% (6 ml) 'until the pH value was 2, and the obtained mixture was extracted with ethyl acetate (100 ml). The organic layer was separated, washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give a colorless oil, and under vacuum, a white foam was obtained. Yield: 93%, 5.9 g.

Analytical data: Silicone (methane / methanol / acetic acid 5/3/1) Rf L 95014 • 253-200529810 1HNMR (DMSO-d6) 12.6 (lH5brs); 7.35 (5H? M); 6.94 (1¾d); 5 ( 2H, s); 4 · 1 (2H, m); 1.4 (9H, s) · Example G.13 2- (Third-butoxycarbamino) -3-pyrazole small group_propionic acid

Intermediates were prepared according to the procedures described in Vederas, 乂 所, C / zern, c., 1985, 707, 7105-7109. Example G.14 1-Methylpyridinyl-hexahydropyridine 4-metanoic acid

Step 1 · Monomethylethoxyquinyl) amino] -hexahydror

Hexahydropyridine-4-carboxylic acid (5 g, 38.7 mmol, 1 equivalent) was dissolved in sodium carbonate / tonight / night (4.5 g, 42.61 mmol, 2.2 equivalents) in 70 ml with 1,4_ Dioxolane (30 liters). A solution of di · tertiary-butyl dicarbonate (9.3 g, 42.61 mmole · 1 si) in 1,4-dioxolane (40 ml) was added dropwise, and the formed The mixture was stirred at room temperature overnight. The organic solvent was removed under reduced pressure, and the resulting solution was acidified with HC1 37% until pH 2 was reached. The obtained suspension was filtered, and the white solid was washed with diethyl ether (5 ml). The mother liquor was 95014-254-200529810 and extracted with ethyl acetate (120 ml), and the aforementioned solid was added. The organic solution was dried over anhydrous sodium sulfate and evaporated under reduced pressure to give a white solid, which was dried at 80 C under vacuum to obtain the title compound. Yield: 93%, 8.2 g. Analytical data: melting point 133-135 ° C. 1H NMR (DMSO-d6) 12 · 3 (1H, br s); 3.85 (2H, d); 2.8 (2H, br); 2.35 (lH, t); 1.8 (2H, d); 1.4 (1 lH, m) · Step 2 · 1-[(1,1-monomethylethoxycarbonyl) amino] -hexahydropyridine

Dissolve 1 [(1,1-dimethylethoxycarbonyl) aminohexahydropyridinecarboxylic acid (6 g '26.16 mmol, 1 equivalent) from step 1 in methanol (150 ml), And carbonic acid shavings (4-26 grams, 13.08 millimoles, 0.5 equivalents) were added. The mixture was stirred at room temperature for 2 hours, and the solvent was removed under reduced pressure. The crude was dissolved in DMF (100 ml) and benzyl bromide (5.37 g, 31.39 mmol, h2 equivalent) was added dropwise. The mixture was stirred at room temperature overnight and poured into water (300 mL) 'and extracted with ethyl acetate (900 mL). The organic layer was dehydrated and dried with anhydrous sodium sulfate 'and evaporated under reduced pressure to obtain a white solid. Yield: 95%, 7 g. Analytical data: 1HNMR (DMSO-d6) 7.3 (5H5m); 5.1 (2H, s); 3.85 (2H, d); 2.8 (2H? Br); 2.65 (lH, t); 1.8 (2H, d); 1.4 (1 lH, m) Step 3: Hexahydropyridine-4-carboxylic acid benzyl ester hydrochloride 95014 -255-200529810

1-[(1,1-Difluorenylethoxycarbonyl) amino] -hexahydropyridine-4-carboxylic acid benzyl ester (7 g, 21_0 mmol) from step 2 was dissolved in 4 ′ Dioxin (20 ml). To this solution, 4NHC1 (7.8 ml, 300 ml, 12 eq.) In 1,4-dioxolane was added, and the resulting solution was stirred at room temperature overnight. The solid was filtered, suspended in n-hexane (50 ml), and filtered to give a white solid. Yield: 54%, 2.5 g. Analytical data1H NMR (DMSO-d6) 8.9 (2H, br); 7.35 (5H, m); 5.1 (2H, s); 3.25 (2H, d); 2.9 (2H, t); 2.75 (1H, m); 2.0 (2H, m); 1.8 (2H, m); Step 4

Dissolve the hexahydrop-bitalate from step 3 (1 g, μmole, 1 equivalent) in DMF (15 ml) and add triethylamine (〇55 Ml, 4 millimoles, 1 equivalent) with gasified methanesulfonium. The mixture was stirred at room temperature for 1 hour and then poured into water (20 ml). The aqueous solution was extracted with ethyl acetate (90 liters), and the organic layer was dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain a colorless oil. Yield: 78%, 0.9 g. Analytical data: 95014 -256-200529810 1H NMR (DMSO-d6) 7.35 (5H, m); 5.1 (2H, s); 3.5 (2H, d); 2.8 (5H, m); 2_6 (1H, m); 2.0 (2H, m); 1.6 (2H, m) _ Step 5: 1-methanesulfonyl-hexahydropyridine 4-carboxylic acid

1-Methanesulfonyl-hexahydropyridine-4-carboxylic acid benzyl ester (0.8 g, 26.7 mmol) from step 4 was dissolved in ethyl acetate (100 ml) and methanol (10 ml). 10% (80 mg) of Pd / C was added and the resulting mixture was hydrogenated at 1 bar. The catalyst was filtered on diatomaceous earth, and the solvent was removed under reduced pressure to obtain a white solid. Yield: 73%, 0.4 g. Analytical data: 1H NMR (DMSO-d6) 12.4 (1H5 br); 3.6 (2H3 d); 2.9 (4H, m); 2.4 (1H? M); 2.0 (2H, m); 1.6 (2H, m) ). Example G.15

Gasification (4-methylphenylureido-dissolve

i-y-c, this compound is made according to / My / zem 1996, double 1243-1252. In short, 'a solution of gasosulfoisocyanate (L62 g, 11.5 mmol, 1 equivalent) was diluted in anhydrous ether, and the resulting solution was made at _50 ° c &lt; T &lt; -4 (Cool under rc. To this solution, p-toluidine (1.23 g, 115 mmol, 1 equivalent) was added. The solution was stirred at -35 ° C for 10 minutes, and a suspension was obtained. 95014 -257- 200529810 The solid was filtered and washed with ether. Yield 80%, 2.3 g. Analytical data: melting point 127-129 ° (: 1H NMR (DMSO-d6) 9.9 (1H, s); 7.3 ( 2H3 d); 7.1 (2H3 d); 2.25 (3H, s); Example G.16 Isopurazol-5-carboxylic acid

〇 HO

The desired carboxylic acid was prepared according to the procedure of Wolfang et al., Doing Xinye, 1986, 69-70. Utilizable compound activity The compounds of the present invention can inhibit the activity of protein degradants. The inscriptions below provide data relating to several example compounds of the present invention, which relate to, for example, the ability to inhibit the activity of protein degradants. Methods and compositions

The compounds of the present invention can inhibit the activity of protein degraders, leading to the inhibition or interruption of various intracellular functions directly or indirectly associated with protein disintegration. In some specific embodiments, the compounds herein can kill tumor cells by inducing: cell> week zero. Therefore, the compounds of the present invention treat cancer, tumors or other proliferative disorders. In further specific implementation of the disintegration function, the hunting is based on the protein structure of the Bensmin compound. Second, it plays a role in the regulation of immune and inflammatory responses and cell viability 95014-258-200529810. Inhibition of proteolytic function can also inhibit the ubiquitination / proteolytic pathway, especially the selective degradation of highly abnormal proteins and transient survival regulating proteins. In some embodiments, the compounds of the invention prevent degradation of p53, which is typically degraded by a ubiquitin-dependent pathway. The ubiquitination / protein hydrolysis pathway also involves the processing of internalized cell or viral antigens into antigenic peptides that bind to MHC-! Molecules. Therefore, the compounds of the present invention can be used to reduce the activity of the cytosolic ATP_ubiquitin-dependent proteolytic system in many types of cells. Thus, the usefulness of such compounds may include therapeutic agents, such as the treatment of various diseases or conditions associated with proteolytic agents. Such methods include administering a therapeutically effective amount of a compound or composition of the invention to a mammal, such as a human, having a disease or disorder associated with a proteolytic enzyme. The wording "therapeutically effective amount" means an amount sufficient to prevent, reduce or ameliorate any phenomenon known in the art to be associated with a disease or condition, such as a cause or symptom. A treatable disease or condition (abnormal physical symptoms) Many diseases or conditions associated with or expected to be treated by causing cell death can be associated with either normal or abnormal activity of either the protein degradation body, such as the regulation of cell decay. These include, for example, Various cancers and tumors' include those associated with the skin, prostate, colorectum, pancreas, kidney, nest, breast, liver, tongue, lung, and smooth muscle tissue. Preferred tumors that can be treated with proteolytic inhibitors include But not limited to hematological tumors such as leukemia, lymphoma, non-Hodgkin lymphoma, bone marrow cells 95014-259-200529810 :, multiple myeloma, and solid tumors such as colorectal, breast, prostate, lung and pancreatic tumors. To elicit a therapeutic effect, protein degradation and / or radiation therapy is administered to the patient. Other antitumor or anticancer agents co-administered by leukocyte degradant inhibitors, examples thereof include, but are not limited to, arsenicin, riamycin, daunorubicin, methotrexate, vincristine Glycans 4, arabinocytosine, cyclophosphamide, hexamethylmelamine, carboplatin, cisplatin, erythromycin t, pachtaxel, and thank you soda (d. cetaxel), Laportiken Gaya, Illinois irmotecam '' gemcitabine, L_pAM, and VP-16. The method of in vitro cell culture is known in the art, And kits are commercially available. See, for example, Ap⑴neTm homogeneous caspase-3 / 7 test, available from Promega Corporation, Hall ㈣, Feng Yiba (Technical Bulletin No. 295, Rev. 2 / 02, Promega) Other diseases or conditions associated with proteolytic bodies, including accelerated or enhanced proteolysis, which occur in atrophic muscles, such as processes that often involve non-lysosomal ATP involving ubiquitin There is a correlation between activation and accelerated or enhanced proteolysis for any of many As a result, this includes septicaemia, burns, trauma, cancer, infections, neurodegenerative diseases such as muscular dystrophy, acidosis or spinal / nerve injury, corticosteroid use, fever, stress, and hunger. Any of a variety of procedures known in the art to test the inhibition of muscle consumption, such as urinary excretion by placing modified amino 3-methylhistamine (see, for example, γ isometric, Federation Proc; 1978, 37, 229). 95014 -260- 200529810

The compounds of the present invention can further be used to treat or prevent diseases or conditions associated with NF- / cB activity, including, for example, human immunodeficiency virus (HIV) infection, and due to, for example, transplant rejection, arthritis, infection, inflammatory bowel disease, Asthma, osteoporosis, osteoarthritis, psoriasis, restenosis and inflammatory conditions caused by autoimmune diseases. Therefore, a method for preventing NF- / CB activation in patients suffering from this disease is therapeutically advantageous. Inhibition of NF- / cB activity can be measured using DNA binding assays such as those described in Palombella et al., 0 // 1994, 7 (5, 773. Generally skilled artisans can easily identify susceptible individuals using standard diagnostic techniques Or individuals suspected of having such a disease or condition.

Example A Detection of chymotrypsinogen-like activity of 20S human erythrocyte protein degradants (HEP) The proteolytic activity of chymotrypsin-like proteins of the compounds of the present invention was measured according to the following procedure. 20S human erythrocyte protein degradants (HEP) purchased from Immatics Biotechnology (Tubingen, Germany) at 0.2 μg / ml (about 0.6 nM catalytic site) at 0.04% SDS 20mM Tris buffer Medium 'was covered in a 96-well microtiter plate. Fluorometer substrate Suc-LLVY-AMC (Poperfluorenyl-Leu-Leu-Val-Tyr-7-acidamino-4-fluorenyl), which will be purchased from Sigma Corporation (St. Louis, MO, USA) Beans) were added to a 10 mM stock solution obtained in the subunit of 曱, the final concentration was 100 // M. The reaction volume was 100 microliters per well. After incubation at 37 ° C for various periods, the concentration of AMC (aminomethylcoumarin) released was determined on a Perkin Elmer HTS 7000 Plus microplate reader to measure 'excitation as 370 nm' and emission as 95014- 261-200529810 465 nm. Proteolytic activity is measured under conditions where the hydrolysis by the mass increases linearly with time, and the change in the fluorescence signal is directly proportional to the concentration of AMC released.

Example B Detection of chymotrypsinogen activity. Bovine α-chymotrypsinogen, purchased from Sigma Company, at 10 ng / ml (about 2PM catalytic site) in 0.5M NaC15mM Hepes buffer #. , Covered in a 9-well microtiter plate. Suc-aaPF_amc, a fluorometer substrate (Succinyl · Qin Shichen refers to progesterinomethyl methyl coumarin), purchased from Sigma (St. Louis, MO, USA) was added to ^^ The stock solution was in dimethylarsine, with a final concentration of 25. The reaction volume was 100 microliters per well. After incubation at room temperature for various periods, the concentration of AMC released was measured on a PerkinElmer HTS 7000P1US microplate reader, with an excitation of 37 nm and an emission of 465 nm. Alpha-chymotrypsinogen activity was measured under conditions in which hydrolytic hydrolysis increased linearly with time, and the change in fluorescence signal was observed to be proportional to the concentration of AMC released.

Example C Determination of IC50 values of ΗEP and chymotrypsinogen inhibitors IC50 values are typically defined as the concentration of compounds necessary to produce 50% inhibition of enzyme activity. The “busy” value is a useful indicator of the activity of a compound for its intended use. If the protein degradant inhibitor of the present invention has an ICSO value of less than about 丨 micromolar for inhibiting human red blood cell protein degrader (HEP), then Can be considered to be active. In some embodiments, the inhibitor does not show some specificity to HEP, and inhibits the burdock chymotrypsinogen 95014 -262- 200529810 1Cso to the redundant 50% inhibition of HEP, This means iC50 (① chymotrypsinogen) / IC50 (HEP), which is greater than about 10. The inhibition of chymotrypsinogen-like activity of HEP and bovine α_chymotrypsinogen is caused by the addition of substrates. Previously, tests were performed by incubating the enzyme with different concentrations of the hypothetical inhibitor at 37. (: incubation for 15 minutes (or chamber / solitary for chymotrypsinogen). Each experimental condition was evaluated in triplicate, and Replication experiments were performed against the inhibitors described herein. If the IC50 value of the compounds of the invention for the inhibition of 系 EP is below 10 ⑻nanomolar ', it is considered to be specific in the tests identified above. Active It is preferred that the compound has an IC50 value of less than 100 nanomolar for the inhibition of HEp. The compound of the present invention more preferably has an IC50 value of less than 10 nanomolar for the inhibition of HEp. In the tests identified above, it has been confirmed that the IC50 value of the compounds of the present invention for the inhibition of HEp is below 1000 nanomolar concentrations.

Example D Cell Detection of Proteolytic Activity Like Proteins in Molt-4 Cell Line

The chymotrypsinogen-like activity of protein degradants in Molt-4 cells (human leukemia) was measured according to the following procedure. A brief description of this method has been previously published (Harding et al., / Mmimo / ·, 1995, / 55, 1767). Molt-4 cells were washed and resuspended in HEpES-buffered saline (5.4 mM KC1, 120 mM NaCl, 25 mM glucose, 15 MgS04, 1 mM pyruvate Na, 20 mM Hepes) and covered. 96-well microtiter white plates to a final concentration of 6 × 10 6 cells / ml. Then, various 5χ proteins were reduced 95014 -263-200529810 disintegration inhibitor concentrate (or diluted DMSO for control group), added to the plate to the final IX concentration, which was diluted by using HEpES-buffered saline 50 times, made from 250X DMSO solution. After incubation at 37 ° C for 15 minutes, the fluorometer cells purchased from the enzyme system product catalog number AFC_88 were transmissible (MeOSuc_FLF_AFC) (methoxysuccinyl-Phe-Leu-Phe-7-fluorenyl _4_ trifluoromethylcoumarin) was added to each well at a final concentration of 25 // M, obtained from a 20 mM stock solution in DMSO. The reaction volume was 100 microliters per well. The concentration of AFC released was on p〇iastar 〇ptima, bmg Labtechnologies microplate_ item picker, using the excitation wavelength of 390 nm and the emission wavelength of 52 () nm, monitoring once every 1.5 minutes, after 30 minutes (22 Cycles). The activity of the protein degrading body is measured under conditions in which the hydrolysis by the mass increases linearly with time, and the change in the fluorescence signal is proportional to the concentration of the APC released.

Example EC0 value determination of proteolytic inhibitor £ CS0 value in EMOLT_4 cell line is typically defined as producing minimal response to enzyme activity inhibition between minimal and aggressive (this test is individually 0% and 85_90% ) Needed to reduce the amount of material. The "EC" value is a useful indicator of the activity of the compound for its intended use. If the compound of the present invention has a redundancy of less than about 10 micromolar, it can be considered as active. The protein-degrading body in MOLT-4 cells is like pancreas. Inhibition of chymosinogen activity was determined by incubating cells with different concentrations of hypothetical inhibitors at 37 C for 15 minutes before adding substrates. Each experimental condition was evaluated in duplicate and replication experiments were performed on The inhibitors described in this article are performed. 95014 -264- 200529810 # HM j M MOLT_4 The EC50 value for protein f degradation inhibitor inhibition is lower than the Mohr concentration, which is considered to be in the test identified above. It is active. The compound of the present invention preferably has a concentration of 2 micrograms for the protein secretion inhibitor EC5G value in the legs. The compound of the present invention more preferably has a heart value of less than 200 milliseconds for the inhibition of protein degradation in MQLT_4. Micromolar concentration. In the tests identified above, it has been stated that the EC value of the compounds of the present invention for inhibition of proteolytic degradation in Mol_4 cells is less than 10 micromolar concentration. Example F Detection of Protease-like Activity of Proteolytic Degradants The trypsin-like activity of human proteolytic agents can be tested as described above with the following modifications. The reaction can be carried out in Tris-glycerin buffer (pH 9.5) supplemented with lmM2-mercaptoethanol, and the substrate can be a fluorescein substrate, such as the oxyquinyl-Phe-Arg-AMC (100 // M ). After incubation at 37 C for various periods, the concentration of AMC released can be measured on a Fluoroskanll spectrophotometer with an excitation filter of 39 nm and a beam of 46.00 mm. It can be measured with a light microscope. Protease activity can be measured under conditions in which the hydrolysis by the mass increases linearly with time, and the change in fluorescence is directly proportional to the concentration of AMC released.

Example G In vivo inhibition of muscle cell breakdown The effect of inhibitors on the unweighted atrophy of soleus muscles in young rats can be determined by, for example, the procedure described in Tischler, Metofem, 1990, 39, 756. For example, juvenile female Sprague_Dawley rats 95014 -265-200529810 (80-90 g) can be cast by the tail as described in Jaspers et al., 乂 物 /, PA㈣ / ·, 1984, 57, 1472 Type, hindlimb suspension. The hind limbs of the animals can be raised above the floor of the cage in which each animal is individually housed. Animals have free access to food and water, and can be weighed during suspension and termination times. During this suspension, animals can be inspected daily to ensure that their toes do not touch the floor of the cage and that the tail does not swell due to the mold. Experimental Design-Part 1 ^ saline ("vehicle") injection. Animals can

Each experiment can start with a suspension of 20 rats, which are randomly divided into 4 groups of 5 animals each. Group A can be suspended for 2 days, providing baseline data on soleus muscle size in other animals that are approximately suspended for longer periods. At the beginning of the study, the average body weight of the groups can be compared and used as a correction factor for body size differences. Group B can be a second control group, which has the soleus muscle of one limb treated with an aqueous solution of amalgam two days after it has not been aggravated, in order to demonstrate the ability to slow the muscle atrophy of each group of animals during the aggravated period. On the second day after the start of unweighting, an aqueous solution of mercury salicylic acid (200 mM; 4 microliters per 100 g of initial body weight) may be injected into a soleus muscle. The contralateral muscle can be maintained for 0.9 spears of the same volume. After injection, the animals were tested with different inhibitors in 95014 200529810. The "η" value is provided to test each inhibitor, and each can be tested in two different transports of the animal. Treatment of soleus muscle —Part 1 After the animal is sacrificed, the sand is fat and connective group beetles and weighed carefully. Then, the muscles can be triturated in 10% trichloroacetic acid (M), and the precipitated by centrifugation. Protein granulation. Then, the pellets can be washed 10% TCA-times, and ethanol :: washing-times. It can be made "

The subsequent pellets were dissolved in 4 ml of 1N sodium hydroxide. Then, the protein content of the sample can be analyzed by using the urease program, using albumin as a standard. Data Analysis-Part 1

The effect of inhibitors on total muscle protein content can be tested primarily by comparison with untreated contralateral muscle pairs. The content ratio can be calculated 'and then analyzed statistically by analysis of variance ("AN0VA"). The left foot can always be treated, so that the protein f content ratio can also be compared with untreated control animals. In this way, significant differences can be shown by comparing: the protein content of the feet and the relative effectiveness of the tested inhibitors. Paired Student trials can also be performed for the effects of separate treatments. Not: The data from the control group also provided an estimate of protein content on day 2. This allows an approximation of the protein changes in each of the B'C and D 'groups within 24 hours of treatment. Test Design—Part 2 * Each experiment can include 10 animals, and 5 animals can be grouped to inhibit the "'rule. Its effect on protein synthesis. This study does not require control animals, because the contralateral Deletion 0 The treated muscles are used as inhibitors to treat the muscle-pairs, groups, groups, groups. Each group can be injected as described in section 丨 about groups C and D. When 95014 -267- 200529810 after the 20th session of treatment Four hours, the fractionation rate of protein synthesis can be analyzed in two soleus muscles. Each muscle can contain 3 H-phenylalanine (50; 1 &quot; Ci / ml) in 0.9% saline solution (3.5 microliters / 100 grams of final body weight) ) Injection. Fifteen minutes later, the middle two-thirds of the muscle can be excised and the muscle can be treated as described below. Treatment of the soleus muscle-part 2

First, the muscles can be washed for 10 minutes in 0.84% saline, which contains 0.5 mM actinomycin to stop protein synthesis, and 20 ^ cycloleucine to capture phenylalanine in the cells. Then, the muscle can be homogenized in 2.5 ml of ice-cold 2% peroxyacid. The precipitated protein can be granulated by centrifugation. One fraction of the supernatant can be used for liquid scintillation counting, and the other fraction can be processed to convert phenylalanine to phenylethylamine, and the soluble phenylalanine concentration can be determined by fluorescence measurement. See, for example, Ga Xian et al., Qin- 乂 1980, / P2,719. These values provide specific intracellular activity. The specific activity of phenylalanine in muscle proteins can be determined after the protein is hydrolyzed by heating in 6NΗα. The released amino acid can be dissolved in a buffer. It is advisable to use “liquid fractions” for scintillation counting, while the other fraction is used to analyze phenylalanine, as the fractionation rate of protein synthesis in the supernatant fraction can be calculated as follows: protein specific activity / intracellular specific activity &quot; between. Data Analysis-Part 2 Protein Shellfish. The analysis can be based on ingredients for each inhibitor. The Student's t-test of the contralateral muscles compared whether the inhibitors had any effect on protein synthesis. The protein fraction and the liver are approximately calculated by the fractionation rate of protein synthesis (obtained from part 2) plus the fractionation rate of protein, and growth (obtained from part 95014 200529810 1), where protein loss is caused by protein growth Negative value. Qualitatively, the ability of inhibitors to slow protein loss without affecting protein synthesis shows a slowdown in protein degradation. Example 之 Anti-tumor activity of living Zhao Nei Research Substances Proteolytic inhibitors for in vivo research can be formulated in appropriate media for intravenous (iv) or oral (PO) administration. For intravenous administration, for example, the compound may be dissolved in a9% Naclf, or administered in a mixture of 09% Nacl, solutol HS15, and dimethylsulfoxide, such as individually in a ratio of 87: 10: 3 (v: v: v). . Cell lines The following human and mouse Zhao tumor cell lines of different histological origin can be used to test the antitumor activity of the compounds of the present invention: H460 (human, lung), A278〇 (human, Inca) ,! &gt; «(human, prostate), L0v〇 (human, colon),

hctU6 (human, colon), BXPC3 (human, pancreas), pANc_i (human, viscera), MX-1 (human, breast), MOLT (human, leukemia), multiple myeloma (human, bone marrow cells) Tumor), YC8 (rat, lymphoma), li2i0 (old breast, leukemia), 3LL (rat, lung). Animal species 5-6 week-old immunocompetent or immunodeprived mice were purchased from commercial sources, such as from Hartan (Correzzana, Mi Italy). The CD1 old-age system is maintained under beneficial conditions; sterilized cages, yarrow, food, and acidified water are used. Implantation and growth of tumor cells 95014 200529810 Solid tumor models of different tissue types (lung, ovary, ^ Zawu, Yue | J column, pancreas, colon) can be transplanted subcutaneously (sc ·) into the axillary region of immunologically active mice ( Rat mode) or immunodeprived mice (human mode). The human tumor cell line originally obtained from ATCC can be modified to grow solid tumors from "in vitro cultures" in vivo. Hematology Tumor model of human or mouse can be transplanted to different locations of immune-active mice (mouse tumors) or immunodeprived mice (human leukemia, lymphoma, and myeloma cell models) according to their highest tumor volume (iv, ip , Hua or sc). Drug treatment Mice with solid (segmented) or hematological tumors were randomly divided into experimental groups (10 mice / group). For solid tumors, the average tumor weight of 0 mg for each group was considered to be the start of treatment; mice with the smallest and largest tumors were discarded. The experimental group was randomly designated as the drug treatment and control group. Animals can be treated intravenously or orally, depending on the oral bioavailability of the compound, and different treatment schedules are known: intravenously or twice a week, or by oral administration per day. ~ In tumor mode, drug treatment can be started after tumor transplantation (day 0) when the tumor size range is between 80-100 mg. The compound can be administered in a suitable solvent at a volume of 10 ml / kg body weight / old rat. Antitumor activity parameters The following parameters can be used to evaluate the estimates of antitumor activity. 95014 200529810 The difference between primary solid tumors and calipers. Du Tianxin Wang Chang, measured in mice twice a week. Monitor;-Survival time of treated mice when delivered to a control group of old-fashioned cars-Weight assessment of individual mice twice a week.

TWI% of tumor growth inhibition (compared with the control group treated with media, the primary tumor growth inhibition is 100%, or in the case of segmented tumors, the relative tumor growth inhibition RTWI% is one week after the last drug treatment The tumor weight (TW) can be calculated as follows: TW = 1/2 ab ^ where a and b are the length and short diameter of the tumor mass, expressed in millimeters. Antitumor activity can be suppressed by tumor weight (TWI %) Determination, which is calculated according to the following formula: 100

TWI% = 100 _ average mean TW RTWI% of the control group (relative percentage of primary tumor growth inhibition compared with the vehicle-treated control group), based on the following formula, one week after the last drug treatment Evaluation:

xlOO where RV _ Vt (tumor weight on day t) 〃 Vo (initial tumor weight at the beginning of treatment) The percentage of tumor regression can be calculated from the perspective of the tumor weight, which is calculated by regression, which is divided by the tumor weight on a specific day The initial tumor weight was determined at the beginning of the experiment. 95014 • 271 · 200529810 In the hematological tumor model, tumor activity can be measured as a percentage increase in the average survival time of mice, which is expressed as the average survival time ratio (τ / c%) of the treatment group (τ) to the control group ⑹. At the end of the experiment (60 days after transplantation), tumor-free animals were excluded from the calculation and considered long-term survivors (LTS). Toxicity assessment in tumor-bearing mice Toxicity can be necropsied Discovery and weight loss based daily assessment. • Old mice were considered dead from toxicity when death occurred before the death of vehicle-treated control animals, or when significant weight loss (&gt; 20%) and / or reduction in spleen and liver size were found. BWC% (% change in body weight) was evaluated as follows: 100 (average mouse weight on a specific day / average weight at the start of treatment) x 100. This value is determined one week after the last treatment with the test compound. Example K In Viability of Cells in Vitro® Measures the redundant value of in vitro viability of cells in the presence of a test compound, which can be determined according to the following procedure. Cells can be seeded in 96_well plates at different densities, and then, After 24 hours, the calcein_AM viability test was used to determine the optimal final density of each cell type. Then, the cells can be tested in 100 microliters of an appropriate cell culture medium known to the artist. At the obtained density, inoculate in a 96-well plate. A serial dilution of the test compound can be made so that the concentration is twice the desired concentration to be evaluated. When 100 microliters of the dilution is then added to cover the 100 When intracellularly in microliter media, final concentrations such as 0, U.7, 46.9, 95014 -272- 200529810 187.5, 375 and 750 nM can be obtained. Compounds can be added to the plate three to four hours after seeding the cells Then, the plate can be cultured at 37t for the desired time point (for example, one, two or three days). Calcein-AM viability test can be performed at the desired time point as described below. Tubes and metal plates are used to aspirate the medium to leave approximately 50 μl / well. The wells can be washed three times with 200 彳 L of DPBS and each time a manifold aspiration is used to leave 50 μl / well. Can be prepared Calcein_AM in DpBS 8 _ Luo solution, and can add 150 microliters to each well. Then the plate can be cultured for 30 minutes under pi. After culture, the calcein can be aspirated by manifold, and can be The cells were washed with 200 microliters of DPBS as described above. After the final aspiration, the fluorescence can be measured using a Cytofluor 2300 fluorescence plate reader. The negative control group can contain the medium without cells, and the experiments can be performed in triplicate.

Example L In Vitro Kinetics Experiments The compounds of the present invention can be tested for proteolytic inhibitory activity using the proposed method described in Rock et al., Ce //, 1994, 761. When the protein degrading body interacts with the test compound to form a complex, according to this procedure, an equilibrium dissociation constant (κ0) is established. The reaction can be performed using SDS-activated 20S protein degrading body obtained from rabbit muscle, and the protein degrading body The substrate can be Suc-LLVY-AMC. Example M. Inhibition of NF- / CB activation. • The compounds of the present invention can be tested for NF inhibition by testing as described in Palombella et al., Ce //, 1994, 78, 773. -/ CB activity. For example,] ^ 〇63 骨 95014 -273-200529810 Cancer cells can be stimulated by treatment with TNFJ. Whole cell extracts can be injured over a specified period of time and migrated by electrophoretic mobility Detection, analysis using pRon probes obtained from the human IFN-10,000 gene promoter. Example N Compound activity

Using the tests of Example C and Example E above, the following Table F-1 confirms the applicability of the compounds of the present invention to the inhibition of protein degradants. In the table below, for the inhibition of HEP, Example C, the compound of the present invention with &quot; + &quot; is less than 1000 nM on the ICw of HEP inhibition; the compound of the present invention with "++" is less than ΐοοηΜ; and Compounds of the invention with "+++" are less than ιηηΜ. In the table below, for the inhibition of MOLT4, Example E, on the ECw of the HEp inhibition, compounds of the invention with + "are less than 1 The compound of the present invention having,, ++, is less than 2-FU; and the compound of the present invention having &quot; parts &quot; is 200 nM. In the case of "&gt; +", the activity is greater than the limit of detection. In the absence of IC50 or EC50 values, data are yet to be determined.

95014 -274- 200529810

D.1.14 ++ &gt; + D.2 +++ +++ D.2.1 +++ ++ D.2.2 +++〉 + D.2.3 +++ +++ D.2.4 +++ ++ + D.2.5 +++ ++ D.2.6 ++ + D.2.7 +++ +++ D.2.8 ++ +++ D.2.9 +++ +++ D.2.10 +++ +++ D.3.1 +++ +++ D.3.2 +++ +++ D.3.3 +++ D.3.7 +++ +++ D.3.8 +++ +++ D.3.11 +++ +++ D.3.12 +++ +++ D.3.15 +++ +++ D.3.24 +++ +++ D.3.26 +++ +++ D.3.27 +++ +++ D. 3.29 +++ +++ D.3.31 ++ ++ D.3.32 +++ +++ D.3.34 +++ +++ D.3.36 +++ +++ D.3.37 +++ +++ D.3.38 +++ +++ D.3.39 +++ +++ D.3.43 +++ +++ D.3.49 +++ ++ D.3.50 +++ +++ D.3.54 +++ +++ D.3.55 +++ +++ D.3.57 +++ +++ D.3.58 +++ +++ D.3.59 +++ ++ D.3.62 +++ +++ D.3.64 +++ +++ D.3.66 +++ +++

95014 -275-200529810

D.3.67 +++ +++ D.3.68 +++ D.3.69 +++ D.3.70 +++ +++ D.3.73 +++ +++ D.3.75 +++ +++ D. 3.76 +++ D.3.77 +++ D.3.78 +++ D.3.80 +++ D.3.87 +++ D.3.89 +++ D.3.91 +++ +++ D.3.92 +++ + ++ D.3.93 +++ +++ D.3.94 +++ +++ D.3.96 +++ +++ D.3.97 +++ +++ D.3.102 +++ ++ D.3.103 + ++ ++ D.3.104 +++ ++ D.3.105 +++ ++ D.3.115 +++ D.3.117 +++ +++ D.3.119 +++ +++ D.3.122 +++ +++ D.3.124 +++ +++ D.3.125 +++ +++ D.3.126 +++ +++ D.3.128 +++ ++ D.3.129 +++ +++ D.3.130 +++ D.3.131 +++ +++ D.3.132 +++ +++ D.3.133 +++ ++ D.3.136 +++ &gt; + D.3.137 ++ + D.3.138 ++ + + D.3.161 +++ ++ D.3.174 ++ +++ D.3.175 ++ D.3.176 +++ +++ 95014 -276- 200529810

D.3.177 D.3.178 D.3.179 D.3.180 D.3.182 D.3.185 D.3.186 D.3.189 D.3.190 D.3.191 D.3.192 D.4.3 D.4.4 D.4.6 D.4.7 D.4.8 D. 4.9 D.6.3 D.6.5D.6.8 D.6.9 D.7.1 D.7.2 D.7.3 D.7.4 D.7.5 D.7.6 D.7.7 D.7.8 D.7.11 D.7.12 D.7.17 D.7.19 D .7.20 D.7.21 D.7.23 D.7.24 D.7.25 D.7.26 D.7.27 D.7.28 D.7.30 +++ ++ +++ +++ +++ ++ +++ +++ ++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

+++ +++ +++

+++ + + +〉 + ++ &gt; + &gt; 4-

+ &gt; + ++ + + + &gt; + ++ + + +〉 +〉 + 95014 -277- 200529810

D.7.31 +++ &gt; + D.7.32 +++ + D.7.33 +++ + D.7.35 +++ &gt; + D.7.36 +++ + D.7.37 +++ &gt; + D. 7.38 +++ ++ D.7.39 +++ + D.7.41 +++ +++ D.7.60 +++ + D.7.61 +++ D.8 +++ +++ D.8.4 ++ + ++ D.8.5 -HH- +++ D.8.6 +++ +++ D.8.18 ++ ++ D.8.19 +++ D.8.20 +++ +++ D.9 +++ D. 12 +++ +++ D.16.6 +++ +++ D.18 +++ +++ D.19 +++ +++ D.24.3 +++ +++ D.24.4 +++ + ++ D.24.6 +++ +++ D.24.8 +++ +++ D.24.9 +++ +++ D.24.10 +++ +++ D.24.11 +++ +++ D.24.12 +++ +++ D.24.14 +++ +++ D.24.15 +++ +++ D.24.16 +++ +++ E.1.1 +++〉 + E.1.2 +++ + E. 1.3 +++ ++ E.1.4 +++ ++ E.1.5 +++ &gt; + E.1.6 ++ + E.1.7 +++ + E.1.8 +++ &gt; +

95014 -278-200529810

95014 E.1.10 +++ E.1.11 +++ ++ E.1.12 +++ &gt; + E.1.13 +++ + E.1.14 +++ E.1.15 +++ ++ E.1.16 ++ + +++ E.1.17 +++ +++ E.1.18 +++ +++ E.1.19 + -H- ++ E.1.20 +++ +++ E.1.21 +++ +++ E .1.22 +++〉 + E.1.23 +++ +++ E.1.24 +++ + -H- E.1.25 -H- + +++ E.1.26 +++ +++ E.1.27 ++ + E.1.28 +++ ++ E.1.29 +++ ++ E.1.30 +++ + E.2.1 +++ +++ E.2.2 +++ ++ E.2.3 +++ + E. 2.4 +++ &gt; + E.2.5 +++ + E.2.6 +++ ++ E.2.7 +++ + E.2.8 +++ + E.2.9 +++ ++ E.2.10 +++ &gt; + E.2.11 +++ &gt; + E.2.12 +++ +++ E.2.13 +++ + E.2.14 +++ &gt; + E.2.15 +++ &gt; + E.2.16 + ++ &gt; + E.2.18 +++ + E.2.19 +++ + E.2.20 +++ + E.2.21 +++ + E.2.22 +++ ++ -279 ·

200529810

E.2.23 +++ ++ E.2.24 +++ &gt; + E.2.25 +++ + E.2.26 +++ &gt; + E.2.27 +++ &gt; + E.2.28 +++ &gt; + E.2.29 +++ + E.2.31 +++ &gt; + E.2.32 +++ &gt; + E.2.33 +++ + E.2.34 +++ + E.2.35 +++ &gt; + E .2.36 +++ &gt; + E.2.37 +++ &gt; + E.2.38 +++ + E.2.39 +++ ++ E.2.40 + E.2.41 +++ &gt; + E.2.42 ++ + &gt; + E.2.45 +++ +++ E.2.46 +++ ++ E.2.47 +++ E.2.48 +++ ++ E.2.49 +++ &gt; + E.2.50 +++ 〉 + E.2.51 ++ &gt; + E.2.52 +++ + E.2.53 ++ &gt; + E.2.54 +++ E.2.55 +++ + E.2.56 +++ + E.2.57 ++ + + E.2.58 +++ + E.2.59 +++ + E.2.60 +++ + E.2.61 +++ + E.2.62 +++ &gt; + E.2.64 +++ &gt; + E. 2.65 ++ &gt; + E.2.66 +++ &gt; + E.2.67 +++ + E.2.68 +++ &gt; +

95014 -280-200529810

E.2.69 +++ &gt; + E.2.70 +++ &gt; + E.2.75 +++〉 + E.2.76 +++ + E.2.77 +++ + E.2.78 + E.2.79 +++ ++ E.2.80 ++ + E.2.81 ++ + E.3 +++ +++ E.3.1 +++ +++ E.3.2 +++ +++ E.3.3 +++ +++ E.3.4 ++ +++ E.3.5 +++ +++ E.3.6 +++ E.3.7 +++ +++ E.3.8 +++ + -H- E.3.9 ++ + +++ E.3.10 +++ +++ E.4 +++ + -h + E.4.1 ++ ++ E.4.2 ++ +++ E.4.3 +++ +++ E.5 + ++ +++ E.5.1 +++ +++ E.5.2 +++ +++ E.5.3 ++ ++ E.5.5 +++ +++ E.5.6 +++ +++ E. 5.7 +++ +++ E.5.8 +++ +++ E.5.9 +++ +++ E.5.10 +++ +++ E.5.11 +++ +++ E.5.12 +++ + ++ E.5.13 +++. +++ E.5.16 +++ +++ E.5.17 +++ ++ E.5.18 +++ +++ E.5.19 +++ +++ E.5.20 +++ +++

95014 -281-200529810

Pharmaceutical Formulations and Formulations When used as a medicine, the compound of formula (1) can be administered as a pharmaceutical composition. These compositions can be administered by a variety of routes including oral, rectal, transdermal, subcutaneous, intravenous, intramuscular, and intranasal, and can be prepared in a manner known in the art of medicine. The present invention also includes a pharmaceutical composition containing one or more of the above-mentioned compounds of formula (1) as an active ingredient, and a combination of one or more pharmaceutically acceptable agents. In making the composition of the present invention, the active ingredient is typically mixed with an excipient, diluted with an excipient, or contained in a carrier such as a capsule, capsule, paper or other container. When the excipient is used as a thin leopard, it may be a solid, semi-solid or liquid f, which is used as an active sword, carrier or medium. Therefore, the composition can be in the form of tablets, pills,

95014 • 282-200529810, night, sugar: ugly agent, suspension, emulsion, solvent: to! Second series (made as a solid or in a liquid medium), containing examples: to: 10% by weight of active compound, ointment, soft and hard gelatin capsules, suppositories, injectable solutions, and aseptic packaging powder forms. At 4 = square, the active compound can be ground to provide the appropriate particle size when combined with other ingredients. Manganese compounds are essentially insoluble

= Can be smashed to a particle size smaller than the fine mesh 4 active compound 1 water soluble on the shell, the particle size can be adjusted by grinding to provide a substantially uniform distribution in the formula, for example about 40 mesh. ^ Some examples of excipients, including lactose, dextrose, saccharose, sucrose, mannitol, starch, acacia, calcium phosphate, sea steamed salt, steam steamed tincture, gelatin, Shi Xi Sour fresh, microcrystalline cellulose, polyvinyl tetrahydropyrrolidone, cellulose, water, syrup and methyl cellulose. These formulations may additionally include: agents such as talc, stearic acid and mineral oil; wetting agents; chemical and suspending agents; preservatives such as methyl parabens and propyl esters; sweeteners and grades Agent. The composition of the present invention can be formulated 'by using procedures known in the art to provide active ingredients after administration to a patient: rapid, sustained or delayed release. Alcohol can be formulated in unit dosage forms, each dosage containing from about 5 to about 100 mg ', more usually about 10 to about 30 mg of active ingredient. "Unit dosage form" is a physically separate unit suitable for use as a single dose for human patients and other mammals. Each unit contains a predetermined amount of active substance calculated to produce the desired / oral effect and is accompanied by The appropriate pharmaceutical excipients are available. The active compounds can effectively cover a wide dosage range, and are generally administered in an effective amount over the pharmaceutical 95014 200529810. However, it should be understood that the amount of compound actually administered is usually based on the physician Related conditional decisions, including symptoms to be treated, the route of administration chosen, the actual compound being administered, the age, weight and response of the individual patient, the severity of the patient's symptoms, etc. For the preparation of solid compositions, such as A tablet is a pre-formulated solid that mixes the main active ingredient with a pharmaceutical excipient to form a homogeneous mixture of the compounds of the present invention. When these pre-formulated compositions are referred to as homogeneous, the active ingredients are typically homogeneous Dispersed throughout the composition so that the composition can be easily subdivided into equivalent effective unit dosage forms, such as tablets , Pills and capsules. This solid pre-formulation is then subdivided into unit dosage forms of the type described above, containing, for example, 0.1 to about 500 mg of the active ingredient of the present invention. The tablets or pills of the present invention may be coated or otherwise blended Formulated to provide a dosage form that will have the benefit of long-term effects. For example, a tablet or pill can contain internal and external dosage components, the latter in the form of an envelope covering the former. The two wounds can be separated by an enteric layer, This layer is designed to prevent disintegration in the stomach and allow the internal components to pass through the duodenum in whole or to be delayed. A variety of substances are available for such enteric layers or coatings, such substances include a variety of polymeric acids 'And mixtures of polymeric acids with substances such as shellac, phositol, and cellulose acetate. The liquid forms in which the compounds and compositions of the present invention can be incorporated for oral administration or by injection' include aqueous solutions, suitably Flavored syrups, aqueous or oily suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil, And tinctures and similar pharmaceutical vehicles 0 95014 -284- 200529810 = compositions for injection or blowing, including solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents or mixtures thereof, and powders: Combination: It may contain appropriate pharmaceutically acceptable positions as described above. In some specific embodiments, the composition is breathed through the mouth or nose: = Drug II provides local or systemic action. The composition may utilize an inert gas Atomization. The atomized a ^ —r- A ^ business gas / liquid can be directly sucked out from the atomization device, or the device can be connected to a mask tent or intermittent force ventilator. Solution, county

The liquid or powder composition can be administered orally or nasally, from a device that is suitable for delivery. The amount of the compound or composition to be administered to the patient will change, depending on the purpose of the second administration of the person being administered, such as prevention or treatment, the state of the patient, and the manner of administration. The i &apos; composition can be administered to a patient already suffering from the disease in an amount sufficient to cure or at least partially suppress the symptoms of the disease and its complications. Enough to achieve such an amount is called &quot; therapeutically effective amount &quot;.Effective; the amount depends on the state of the disease being treated, and by the responsible clinician: the judgment 'depends on a number of factors, such as the severity of the disease, the age, weight, and general state of the patient. 7 Injected: The composition of the patient may be in the form of the above-mentioned pharmaceutical composition. These compositions can be sterilized using conventional sterilization techniques or can be sterilized and filtered. The aqueous solution can be used as it is, or used as a dry preparation, which is combined with a sterile aqueous carrier before administration. The compound formulation value is typically between 3 and 1 ', more preferably 5 to 9, and most preferably ⑴. As the sun and the moon progress, the use of some of the aforementioned excipients, vehicles, or stabilizers will cause the formation of medicinal sleep. 95014 -285-200529810 The therapeutic dose of the compound of the present invention can be changed according to, for example, the specific application for which the treatment is to be administered, the manner in which the compound is administered, the health and condition of the patient, and the judgment of a designated physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending on a number of factors, including dosage, chemical characteristics (e.g., hydrophobicity), and administration.

Drug route. For example, a compound of the invention may be provided in a physiological buffer solution, which contains about 0.1 to about 10% w / v compound for parenteral administration. Some typical doses range from about 1 μg / kg to about 1 g / kg of body weight per day. In some embodiments, the dosage ranges from about 0.1 mg / kg to about 100 mg / kg body weight per day. Dosage also depends on variables such as the type and extent of disease or condition progression, the overall health of the particular patient, the relative biological efficacy of the selected compound, the formulation of the excipient, and the route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems. The invention also includes a pharmaceutical kit &apos; that can be used, for example, to treat or prevent an inflammatory disease, which comprises one or more containers containing a pharmaceutical composition containing a therapeutically effective amount of a compound of formula ω. If desired, such a kit may further include one or more different conventional pharmaceutical kit ingredients, such as containers with one or more pharmaceutically acceptable carriers, other containers, etc., which are well known to those skilled in the art. Instructions, no inserts, inserts, or labels. Dai Xian does not want to be administered ingredients, guidelines for investment, and also quoting and / or mixing ingredients, can also be included in the kit. Various modifications of the present invention, except for those described herein, which are derived from A &gt; will become apparent for the acquaintances. Such amendments are also intended to fall within the range of ° attached to the article. Reference materials cited in this petition include 95014 200529810, including patents, published patent applications, and journal articles, which are incorporated by reference in their entirety.

95014 -287-

Claims (1)

200529810 10. Scope of patent application 1. A compound of formula (I) X Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, in which R is C! -Cg alkyl, c: 2-C8 alkenyl, C2-C8 alkynyl, or C3-C7 cycloalkyl ; R2 is Η,-(CH2) aCH2NHC (= NR4) NH-Y,-(CH2) bCH2CONR5R6,-(CH2) c CH2 N (R4) CONH2 ^-(CH2) d CH (R7) NR9 R1 〇 ^- (CH2) eCH (R7) ZR8; 冱, 13 and (: each independently is 0, 1, 2, 3, 4, 5, or 6; d and e are each independently 0, 1, 2, 3, or 4; R4 is Alkyl; R5 and R6 are each independently fluorene, q -C! G alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or 'R5 and R6 and their attached u atoms together form a heterocarbocyclic ring R7 is fluorene or CVCw alkyl; R8 is fluorene or CA. Alkyl, n-based, aryl groups such as, Η? NS (= 0) 2 _, -SO3 Η or protecting group; R9 is Η, Ci -Cw alkyl, carbocyclyl or heterocarbocyclyl; Ri0 is fluorene, CAo alkyl, disc ring, heterocarbocyclyl, alkyl, C2-ClO di-c (= 0) _, C2_Ci 〇 Block-based group-㈣-, heterocarbon ring group evaluation 〇) _, carbocyclic group base ((which, hetero95014 200529810 carbocyclic group base-C (= 0)-, Ci_Ci〇 alkyl-S (= 0) 2-, %%-S (= 0) 2 _, heterocarbocyclyl- S (= 0) r, carbocyclylalkyl_s (= 0) 2-, heterocarbocycloalkyl-S (= 0) 2-, Ci-Cioalkyl-NHC (= 0)-, carbon Cyclo-NHC (= 0)-, Heterocarbocycline · NHC (= 0)-, Carbocycloalkyl-NHC (= 0)-, Heterocarbocycloalkyl-NHC (= 0)-, Q 〇 alkyl-0C (= 0)-, carbocyclyl-0C (= 0)-., Heterocarbocyclyl-0C (= 0)-, carbocyclyl-0C (= 0)-, heterocarbon Cycloalkyl-0C (= 0) _, Ci 0 alkyl-NH-C (= 0) -NHS (= 0) 2-, carbocyclyl-NH-C (= 0) -NHS (= 0) 2-, Heterocarbocyclyl-NH-C (= 0)-φ NHS (= 0) 2-, Ci-Cio alkyl · 8 (= 0) 2_ΝΗ- (3 (= 0)-, Carbocyclyl- S (= 0) 2 -NH-C (= 0)-, heterocarbocyclyl-S (= 0) 2 · NΗ-(: (= 0)-or amine protecting group; where R1 G is optionally 1, 2, or 3 R23 substitutions; or, R9, together with R1G and the N atom to which they are attached, form a heterocarbocyclyl, optionally substituted by 1, 2 or 3 R23; Y is Η, _CN, -N02, -SpOhR11 or guanidino protecting group; alkyl, aryl or NR12R13; R12 and Ri3 are independently fluorene, Cl_ClG alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or, R12 and R13 and each other And other connected atoms together to form a heterocarbocyclic group; Z is 0, s, Se or Te; Q is -B (OH) 2, -B (OR14) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dibasic borane ester contains 2 to 20 carbon atoms, and optionally contains a hetero atom which may be N, S or 0 R is fluorene, q-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; 95014 -2- 200529810 X is RAC (= 〇)-, ranhc (= o)-, ras (= o) 2-, ra〇c (= o)-, rasc (= o)-, or RA; RA is Ci-CM alkyl substituted with R20 as appropriate; C2-C2G alkenyl substituted with R2G as appropriate ; C2-c2 () alkynyl optionally substituted by r2G; carbocyclic optionally substituted by 1-5 R21; or heterocarbocyclic optionally substituted by 1-5 R21; φ R2G is selected from Including: -CN, i group, -alkyl-, Ci-q alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (= 〇) NH2, -S (= 0) 2NH2, -OH, _SH, -NH2, _NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0) R2 () a, -NHC (= O) OR20a, -OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -s (= 0) 2 R2 0 a, -s (= 0) 2 -NHR2 0 a, -SC (= O) R20a ^ -C (= O) R20a ^ -C (= O) NHR20a ^ -C (= O) O-R20a ' -NHS (= 0) 2R2Ga, -NHR2Gb, o-phthalenedia Amine,-(0-alkylfluorenyl) r-OH,-(0-alkyl) r- (0-alkyl), -OR2Gc, -SR2Ge, -O-alkyl-R2Gc, -S · Alkyl-R2Gc, -S (= O) -R20c, -S (= O) 2-R20c, -S (= O) 2-NHR20c, -SCpCOR20. , -C (= O) R20c, -C (= O) OR20c, -C (= 0) NHR2Ge, a carbocyclic group substituted with 1-5 R21 as appropriate; and optionally substituted with 1-5 R21 Heterocarbocyclyl; alkyl 'C2-C20 alkenyl or C2-C20 alkynyl; where the alkyl, alkenyl or alkynyl is optionally one or more halo, OH'CN'Ci-q alkane Group, Ci-q alkoxy group, C2-C8 alkoxy alkoxy group, aryl group, heteroaryl group or -NHR2Gb; 95014 200529810 R2 () bg amine protecting group; R20e is optionally substituted by 1-5 R22 A carbocyclic group; or a heterocarbocyclic group optionally substituted with 1-5 R22; R2 1 is selected from the group consisting of: Ci -C2o alkyl, C2-C2o alkenyl, C2_C2o alkynyl, -o R21 a, -SR21 a, -CN, halo, haloalkyl, -NH2, -NH (alkyl), _N (alkyl) 2 -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -c〇OH, -C (= 0) 0-alkyl, -C (= 0) alkyl, -C (0) H, -S (= 0) -alkyl, · 3 (= 〇) 2-alkyl, _s (= 0) _aryl, -S (= 0) 2 • Aryl, optionally 1-5 R2 2 Substituted carbocyclyl, and optionally a heterocarbocyclyl substituted with 1-5 R22; R21a is fluorene, CrCw alkyl, C2-C2o alkenyl, c2-C2o alkynyl, carbocyclyl or heterocarbon Ring group; R22 is selected from the group consisting of: CVCw alkyl, C2-C10 alkenyl, C2-C10 alkynyl, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, and amine Diamine, carboxyl, alkyl-oc (= o)-, alkyl-C (= 0), aryl-0C (= 0)-, alkyl-0C (= 0) NH-, Aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (alkyl-0) r-alkyl, HO- (alkyl- 0) r-alkyl-, -OH, -SH, -CN, -N3, _CNO, -CNS, alkyl-S (= 0)-, alkyl-s (o) 2-, H2NS (= 0) -And H2NS (= 0) 2-; R23 is selected from the group consisting of: CVQ alkyl, C2-C6 alkenyl, C2-C6 alkynyl, F, Cl, B1, I, haloalkyl, -NH2, -NHR23a,- N (R23a) 2, -N3, -N02, -CN, -CNO, -CNS, -C (= 0) 0R23a, -C (= 0) R23a, -0C (= 0) R23a, 9501 4 200529810 -N (R23a) C (= 0) R23a, -N (R23a) C (= 0) 〇R23a, -C (= 0) N (R23a) 2, ureido, -OR2 3 a, -SR2 3 a, -SpOHq _C6 alkyl), -S (= 0) 2-(CrC6 alkyl), -S (= 0) -aryl, -S (= 0) 2_aryl, -S (= 0) 2-N (R23a) 2; optionally a carbocyclic group substituted with 1-5 R24; and optionally a heterocarbocyclic group substituted with 1-5 R24; &amp; 23 &amp; is [[or (31 &lt;: 6 alkyl; Alternatively, two R23a may be combined with the N atom to which they are attached to form a 5 to 7-membered heterocyclic group in%; and R24 is selected from the group consisting of: cvc4 alkyl, c2-c4 ene Group, c2-c4 alkynyl, phenyl, i-based, haloalkyl, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, carboxy, alkyl-oc (= o) _ , Alkyl &lt; (= 〇)-, aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-〇c (= 〇) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (carbyl_0) r_alkyl, ho- (carbonyl_0) r_alkyl-, -OH, -SH, -CN, -N3, _CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, ^% NSpO}-, and H2 NS (= 〇) 2 _; and 1, 2, 3 , 4,5,6,7,8,9 or 10; with the condition that 'When Q is shan 2,2-tetramethylethane When diol dihydroxyborane is purported, then X is not an aralkyloxycarbonyl group; the condition is that when Q is tetramethylethanediol dihydroxyborane and R1 is a cycloalkyl group, then R2 is not -CH2 c0nh2; and the condition is that 'When X is rac (= 〇)-, rA is a C4_Ci5 linear alkyl group substituted with R20, and R20 is -CN ... c2H ,, _NHS (= 〇) 2R2 () a, or phthalimidine 95014 200529810 imine group; then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where Y is Η, _CN, -N02 or Pulse base protecting group. 2. The compound of claim 1, wherein Ri is Ci_C4 alkyl. 3. A compound as described in item 1, wherein R1 is 2-propyl. 4. The compound of claim i, wherein R2 is &lt; CH2) aCH2NHC (= NR4) NH Y, • (CH2) bCH2CONR5R6,-(CH2) cCH2N (R4) CONH2, _ (CH2) d CH (R7) NR9 R10 or _ (Ch2) e ch (r7) zr8. 5. The compound according to item 1, wherein R2 is-(CH2) aCH2NHC (= NR4) NH-Y. 6. A compound according to item 5, wherein a is 1, 2, 3 or 4. 7. A compound according to claim 5, wherein a is 2. 8. The compound of claim 1, wherein R2 is _ (CH2) dCH (R7) NR9R10. 9. The compound of item 8 as in β month, wherein d is 0, 1 or 2 0 10 The compound of item 8 as in claim d, where d is 0. U. Compounds such as May seeking item 8, wherein R9 is Η. 12. A compound as described in δ Month 1, wherein R2 is-(CH2) eCH (R7) ZR8. 13. The compound of claim 12, wherein z is 0. 14. A compound as claimed in claim B, wherein e is 0, 1 or 2. 15. A compound according to claim 13, wherein e is 0. A compound with a term of 16 ^, where 卩 is called Oyin 2 or a cyclic dihydroxyborane-"wherein the cyclic disulphoyl ester contains at least 10 carbon atoms and contains at least one cycloalkyl group Partial groups. 17. Shi Ming compound of item 16, where Q is spinach diol dimer radical burning vinegar. 18 · compound of item 16 'It is dicyclohexyl #diol dimer borane _. 95014 200529810 19 · The compound of claim 16, wherein q is 丨, 孓 dicyclohexyl-ethane j, 2-diol dihydroxyborane ester. 20 · The compound of claim 1, wherein X is rac (= 〇)-. 21. The compound as claimed in claim 1, wherein X is ranhc (= 0)-. 22. The compound as claimed in claim 1, wherein X is ras (= 〇) 2_. 23_ As claimed in claim 1. A compound in which rA is a Ci-C &quot; alkyl group substituted with-(〇-alkyl) "OH or alkyl" -O-alkyl), wherein 1 "is 1, 2, 3, 4 or 5. φ 24. The compound as claimed in claim 23, wherein ra is an alkyl group substituted with alkyl) r_OH,-(0-alkyl) r (0-alkyl), wherein r is 1, 2 or 3. 25. The compound of claim 23, wherein rA contains at least one -CH2ch2 〇_ group. 26. The compound of claim 23, wherein # is _CH2 (〇CH2cH2) r〇CH3. 27. The compound of claim 23, wherein ra is -CH2 〇CH2 ch2 〇CH2 ch2 〇CH3 or -ch2〇ch2ch2och3. 28. If the compound of claim i, wherein ra is aryl or heteroaryl, each optionally substituted by 1 to 5 R21. 29. If the compound of claim !, wherein ra is cycloalkyl or Heterocycloalkyl, each optionally substituted by 1 to 5 R21. 3．As the compound of claim !, wherein ra is Ci-Cw alkyl; c2-Cw alkenyl; or C2-C2alkynyl, each optionally Substituted by R2G. 31. The compound according to claim !, wherein ra is Ci-C2O alkyl; heptadecenyl; or C2 heptynyl, each substituted with a carbocyclyl or heterocarbocyclyl, wherein A cyclic or heterocarbocyclyl is optionally substituted with 1, 2 or 3 R21. 32. The compound of claim 1, wherein ... is ^ alkyl to alkyl; alkenyl; 95014 200529810 or A-Cm alkynyl , Each being substituted by an aryl group, wherein the aryl group is optionally substituted by i, 2 or 3 R2 1. 33. The compound according to claim !, wherein Ra is Ci_C2G alkyl group; c2_C2G alkenyl group; Or Q-Cm alkynyl, each substituted with a heteroaryl, wherein the heteroaryl is optionally substituted with 1, 2, or 3 R2 1. 34. Compounds as claimed in claim, wherein ra is Ci_C2O alkyl; Alkenyl; or alkynyl, each substituted with a cycloalkyl, where the cycloalkyl is optionally substituted with 1, 2 or 3 R21. 35 · If requested! Compounds in which Ra is Ci_C2G alkyl; C2_Cm alkenyl; or C2-C: 2 alkynyl 'are each substituted by a heterocyclic alkyl group, wherein the heterocyclic alkyl group is optionally substituted with 1, 2 or 3 R21 . 36. The compound of claim 1, wherein r2 is -CH2NH-C (= 〇) 〇ch2 (C6H5). 37. The compound according to claim}, wherein Ra is Ci_C2O alkyl; C2-C2 () alkenyl; or C2-C2 () alkynyl, each optionally substituted by R2G, wherein r2O is selected from CN and halogen Base, haloalkyl, -C02H, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, Lu-S (= 0) NH2, -S (= 0) 2NH2 -OH, _SH, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= O) R20a, -NHC (= O) OR20a, -OR20a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= 0) 2 -NHR2 0 a, -SC (= 0) R2 0 a, -C (= 0) R20 ^. -C (= O) NHR20a &gt; -C (= O) O-R20a ^ -NHS (= 0) 2 R2 0 a ^ -NHR2Gb, phthalimide,- (〇-alkyl),-(〇-alkyl) r-OH,-(〇-alkyl) Γ- (0-alkyl), -OR20c, -SR20c, -0-alkyl-R20c, each Radical_R2 0 c, -S (= 〇) -R2 0 c, -S (= 0) 2 -R2 0 c, -S (= 0) 2 -NHR2 0 c, -SC (= 0) R2 0 c , -C (= O) R20c, -C (= O) OR20K (= O) NHR20c. 38. A compound according to claim i, wherein R2 is H and X is (O-alkyl)-(〇-alkyl95014 200529810) r- (CrC14 alkyl) -C (= 0)-or HO- (alkane -OWCVCm alkyl) _c (= o) ... 39. As in the compound of claim 1, where χ is RAq = 0)-, and RA is c4_CM alkyl. 40. The compound of claim 1, wherein X is κA (:: (= 〇)-, and # is an aryl group optionally substituted with 1 to 3 R2 1s. 41. The compound of claim 1, wherein X is rac (= 〇) _; rA is a benzyl group substituted with one R2 i φ; and R21 is a phenoxy group. 42. The compound of claim 1, wherein X is RAC (= 0) ·, and RA is R2. Substituted ^ 4-alkyl, and R2O are aryl groups optionally substituted by "个] ^! 43. The compound of claim 40, wherein the aryl group is substituted with at least one halo group. 44. If requested The compound of item 1, wherein X is RAC (= 0)-; RA is Ci'ci4 alkyl substituted by R2O; and R20 is -OR20a4-OR20c. 45. The compound of claim 1, wherein X is RAC ( = 0)-; RA is Ci 4 alkyl substituted with R 2 0; and R 2 G is a heterocarbocyclic group optionally substituted with 1 to 3 R 21. _ 46. The compound according to claim 1, wherein X is RaS ( = 0) 2- and Ra is c3-cl6 alkyl. 47. A compound of formula (I) as claimed in claim 1: R1 is C or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein i-c8 alkyl, c2-c8 alkenyl, c2-c8 alkynyl, or cvcyf alkyl; 95014 200529810 R2 is Η,-(CH2) aCH2NHC (= NR4) NH-Y,-(CH2) bCH2CONR5R6,-(CH2) c CH2 N (R4) CONH2,-(CH2) d CH (R7) NR9 R10 or-(CH2) eCH (R7) ZR8; Wang, 13 and. Each independently is 0, 1, 2, 3, 4, 5, or 6; d and e are each independently 0, 1, 2, 3, or 4; R4 is 11 or (^-(: 1 () alkyl; R5 and R6 is each independently fluorene, Q-Cm alkyl, carbocyclyl, heterocarbocyclyl or amine protecting group; or, R5 and R6 and the N atom to which they are attached together form a heterocarbocyclyl; R7 is fluorene or CVCw alkyl; R8 is fluorene, Ci-Cio alkyl, alkyl_s (= 〇) 2-, aryl name (= 〇) 2-, H2NS (= 0) 2-, -S03H or protecting group; R9 Is fluorene, Ci-Cio alkyl, carbocyclyl or heterocarbocyclyl; R10 is fluorene, q-Cw alkyl, carbocyclyl, heterocarbocyclyl, Ci_Cio alkyl-c (= 0)-, carbon Cyclo-c (= 0>, heterocarbocyclyl_c (= 〇) _, carbocyclylalkyl-CK »-, heterocarbocyclyl_c (where, Ci_CiGalkynyl · s ( = 〇) 2 _, carbocyclyl-s (= 〇) 2_, heterocarbocyclyl_s (= 〇) 2_, carbocyclylalkyl-s (= 0) 2-, heterocarbocyclyl group_ s (= 〇) 2-, Ci_Ci () alkyl-NHC (= 〇)-, carbocyclyl_NHC (which, heterocarbocycline (= 〇), carbocyclyl-NHCH », heterocarbon Cycloalkyl_stomach (= 〇) _, Ci_c ^ alkyl-OC (= G) ·, carbocyclyl_Qq which is called heterocarbon county = 〇), carbocyclyl-0C (= 0) -、 Heterocyclic carbon 〇c (Which or amine protecting group; where Ri0 is optionally substituted by i, 2 or 3 like 23; or, R9 and the heart and the N atom to which they are connected together to form a heterocarbocyclic group; 95014 200529810 Y Is · H, -CN, -N〇2, -s (= 〇) 2Ru or guanidino protecting group; R is C! -C6 alkyl, aryl or NRl 2 Rl 3; Rl2 and R13 are independently H, CrCM enthalpy: ^ T-poor 1 ClG alkyl, sulfonyl, heterocarbocyclic or amine protecting group; or, RU together with the atoms to which they are attached form a heterocarbocyclic group; z is 0, s, Se or Te; soil Q is -b (0H) 2, _b (orm) 2 or cyclic dihydroxyborane vinegar, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains one which can be N, S Or a heteroatom of 0; R14 is Η, q-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl; X is RAC (= 0)-, RaNHC (which, ras (= 〇 ) 2 "ra〇c (= 〇) _, or Ra; RA is a Qo alkyl group optionally substituted by R2G; C2-C2o alkenyl group optionally substituted by R2G; C2_C2Q, optionally substituted by R2G Alkynyl; carbocyclic groups optionally substituted with 1-5 R21; or heterocarbocyclic groups optionally substituted with 1-5 R21; R2 () is selected from the group consisting of: -CN, i group, i alkyl ·, Ci-q alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -co2h, -c (= o) co2h, -C (= 0) NH2, -C (= 0) H, -S ( = 0) NH2, -S (= 0) 2NH2, -OH, -SH, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0 ) R2〇a, -NHC (= 〇) 〇R20a, OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= 〇) 2 -NHR2 0 a, 95014 -11-200529810 _SC (= 0) R2〇a, -C (= O) R20a, -C (= 0) NHR2〇a, -C (= 〇) 〇-R20a, -NHS (= 0) 2R2 () a, -NHR2 0b, phthalimide, alkyl) Γ, -0-alkyl-OH,-(0-alkyl) r-OH, -OR2Gc, -SR2Gc, -0-alkyl, each alkyl _R2Gc, _s (= 〇) _R2 () c, -Sp〇) 2-R20c, -S (= O) 2-NHR20c, -SC (= O) R20c, -C (= O) R20c, -c ( = o) or20c, -C (= 0) NHR2Ge, carbocyclic groups optionally substituted with 1-5 R21; and heterocarbocyclic groups optionally substituted with 1-5 R21; Alkyl, C2-C20 dilute or C2-C20 alkynyl; wherein the alkyl, fine or fast is optionally one or more halo, Ci-C4 alkyl, aryl, heteroaryl or- NHR2Gb substitution; R2 G b is an amine protecting group; R2Ge is a carbocyclic group optionally substituted with 1-5 R22; or a heterocarbocyclic group optionally substituted with 1-5 R2 2; R21 is selected from the group consisting of : Ci-Cw alkyl, C2-C2o alkenyl, C2-C2G alkynyl, q-Cw alkoxy, Ci -C2Q thioloxy, -OH, -CN, _ group, _alkyl, -NH2 , -NH (alkyl), -N (alkyl), -NHC (= 〇) 〇-alkyl, -NHC (= 0) alkyl, C (= 0) 0-alkyl, -C ( = 0) alkyl, -s (= 0) -alkyl, -s (= 0) 2-alkyl, -S (= 0) -aryl, -S (= 0) 2-aryl, as appropriate Carbocyclyl substituted with 1-5 R22; and heterocarbocyclyl substituted with 1-5 R22 as appropriate; R22 is selected from the group consisting of: Ci-C1Q alkyl, C2-C1 () alkenyl, C2- C1 () alkynyl, phenyl, [§yl, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, alkyl-OC (= 〇)- , Alkyl-c (= 0)-, aryl-〇C (= 0)-, 95014 -12- 200529810 alkyl-0C (= 0) NH ·, aryl-〇C (= 0) N H_, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (carbyl-〇) r-alkyl, oxo- (carbyl-0) r-alkyl, -OH , -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2NS (= 0) _ &amp; H2NS (= 0) 2 -; R23 is selected from the group consisting of: Ci-C6 alkyl, C2-C6 alkenyl, c2-c6 alkynyl, F, Cl, Br, I, haloalkyl, -NH2, -NHR23a, -N (R23a) 2, -N3, -N02,- CN, -CNO, -CNS, -C (= 〇) 〇R23a, -C (= 0) R23a, -0C (= 0) R23a, -N (R23a) C (= 0) R23a, _c (= 0) N (R23a) 2, ureido, -OR23a, -SR23a, 4 (= 0) 2-((^-c6 alkyl), -s (= 0) 2-aryl, and -S (= 0) 2- N (R23a) 2; alkyl; or 'two R23a may be combined with the N atom to which they are attached to form a 5- to 7-membered heterocyclic group; and 1: is 2,3,4,5 , 6,7,8,9 or 10; and with the proviso that when Q is u, 2,2-tetramethylethanediol dihydroxyborane vinegar, then X is not an aralkyloxycarbonyl group ; Its additional condition is 'When Q is U, 2,2-tetramethylethanediol dihydroxyborane vinegar' and R1 is a cycloalkyl group, then R2 is not -CH2CONH2; and its additional condition is , When X is rac (= 〇)-, rA is a C4-Ci5 linear alkyl group substituted by 圮 〇, and R20 is _CN ... c〇2H,, -NHS (= 0) 2R2〇a, -NHC (= O) R20a, -NHR20b or phthalimidine imide; then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where Y is Η, -CN, · ν〇2 or guanidine Base protection base. 950U -13- 200529810 48. The compound of claim 47, wherein R1 is 2-propyl. 49. The compound of claim 47, where Q is _b (OH) 2. 50. The compound of claim 47, of which Q is a pinanediol dihydroxyborane ester. 51. The compound of claim 47, wherein X is rAc (= 〇)-. 52. The compound of claim 47, wherein 圮 is _CH2NH_C (= 0) 0CH2 (C6H5). 53. The compound of claim 47, wherein X is rAC (= 0>, and ra is C4_c "alkyl. 54. The compound of claim 47, wherein X is raC (= 〇) _, And # is an aryl group optionally substituted by 1-3 RUs. 55. The compound of claim 47, wherein X is rAC (= 〇)-, and ra is a heterocarbocyclic ring optionally substituted with 1-3 R2 1 56. The compound of claim 47, or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is 2-propyl; R2 is hydrazone,-(CH2) aCH2NHC (= NR4 ) NH-Y,-(CH2) bCH2CONR5R6, #-(CH2) c CH2 N (R4) CONH2,-(CH2) d CH (R7) NR9 R1 G &lt;-(CH2) eCH (R7) ZR8; Q is -b (oh) 2 or pinanediol dihydroxyborane; X is RAC (= 0)-; and RAgQ-Ci6 alkyl; An aryl group substituted with 1-3 R21 in the case; or a heterocarbocyclic group substituted with 1-3 R2 1 in the case. 57. A compound of formula (I) as claimed in claim 1: 95014 -14- 200529810 Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is cvc8 alkyl; R ^ _ (CH2) aCH2 ^ C (= NH) NH-Y,-(CH2) cCH2NHCONH2, -(CH2) d CH (R7) NR9 R10 or-(CH2) e CH (R7) ZR8; a is 1, 2, 3, 4 or 5; c is 1, 2, 3, 4 or 5; d is 〇, 1 or 2; e is 0, 1 or 2; R7 is H or methyl; R8 is fluorene, CVCw alkyl, -s (= 0) 2-alkyl, -s (= o) 2-aryl , -S (= 0) 2 -NH2, -SO3 H or protecting group; Y is -Η, -CN, -N02, -SK ^ R11 or guanidyl protecting group; R9 is Η, alkyl, carbocyclyl Or heterocarbocyclyl; R1 () is fluorene, (VC1 () alkyl, carbocyclyl, heterocarbocyclyl, q-Cw alkyl-C (= 0)-, carbocyclyl-C (= 〇) -, Heterocarbocyclyl-C (= 0)-, carbocyclylalkyl-C (= 0)-, heterocarbocyclyl-c (= o)-, q-C! 〇carbyl-S (= 0) 2-, Carbonyl-S (= 0) 2-, Heterocyclyl-S (= 〇) 2-, Carbocyclyl-8 (= 0) 2-, Heterocarbyl Carbo-S (= 0) 2-, Cl-Cio-Hexyl-NHC (= 〇)-, Carbocyclyl-NHC (= 0)-, Heterocarbocyclyl-NHC (= 0)-, Carbocyclyl Alkyl_NHC (= 0)-, Heterocyclic alkyl-NHC (= 0)-, CVQo 95014 -15-200529810 Alkyl-0C (= 0) »·, Carbocyclyl_oc (= 〇 ) _, Carbocyclylalkyl-oc (= o) _, heterocarbon protecting group; where R10 is optionally 1, or R9 and R1G and the original R1 to which they are connected C! -C6 alkyl, aryl or NR1 2 R1 3; bad alkyl-0C (= 0) _ or amino group 2 or 3 R2 3 substitutions; together form a heterocarbocyclic group; a protecting group; Carbocyclyl, heterocarbocyclyl or amine Alternatively, R4R13 and the u atom to which they are attached together form a heterocarbocyclic group; 2 is 0 or S; Q is -B (OH) 2, -B (OR14) 2 or a cyclic dihydroxyborane ester, wherein the cyclic dibasic side alkyl ester contains 6 to 20 carbon atoms and contains at least one cycloalkyl moiety Part of the group; R is fluorene, C! -C4 alkyl or cycloalkyl; X is RACH))-, RAnHC (= 0)-, RASH)) 〇) _ or ra; RA is a CVC20 alkyl group optionally substituted by r2G; C2-C2 0 alkenyl group optionally substituted by R2 G; C2-C2G alkynyl group optionally substituted by R2G; optionally a carbocyclic ring substituted by 1-5 R21 Or a heterocarbocyclic group optionally substituted with 1-5 R21; R2Q is selected from the group consisting of: -CN, _yl, haloalkyl, alkyl, c2_c4 alkenyl, C2-C4 alkynyl, -C02H , -C (= 0) C02H, _c (= 0) NH2, -c (= o) h, -S (= 0) NH2, -S (= 0) 2NH2, -OH, -SH, -NH2,- NH (alkyl), 95014 -16- 200529810 -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 0) R2Ga, -NHC (= O) OR20a, -OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= 0) 2 -NHR2 0 a, _SC (= O) R20a, -C (= O) R20a , -C (= O) NHR20a, -C (= O) 〇-R20a, -NHS (= O) 2R20a, -NHR20b, phthalimide,-(〇-alkyl) Γ, -〇 -Alkyl_OH,-(0-alkyl) Γ-ΟΗ, _OR20c, -SR2 () e, -0-alkyl-R20c, -S-alkyl-R20c, -S (= O) -R20c,- s (= o) 2-r20c, -S (= O) 2-NHR20c &gt; -SC (= O) R20c ^ -C (= O) R20c &gt; -C (= O) OR20c '-C (= 0 ) NHR2Ge, a carbocyclic group substituted with 1-5 R2 1 as appropriate; and a heterocarbon substituted with 1-5 R21, optionally with φ Alkyl, C2-C20 alkenyl or C2-C20 alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally one or more halo, CrC4 alkyl, aryl, heteroaryl or- NHR2Gb substitution; R2 () b is an amine protecting group; R2Ge is a carbocyclic group optionally substituted by 1-5 R22; or a heterocarbocyclic group optionally substituted by 1-5 R22; R21 is selected from the group consisting of : Cl-C2o alkyl, C2 (20 dialkyl, C2-C2o alkyl, Ci (2o alkyl, CVC20 thioalkoxy, -OH, -CN, halo, haloalkyl, -NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 0) 0-alkyl,- C (= 〇) alkyl, -S (= 0) -alkyl, -S (= 0) 2-alkyl, -S (= 0) aryl, -S (= 0) 2-aryl, Optionally a carbocyclic group substituted with 1-5 R22, and optionally a heterocarbocyclic group substituted with 1-5 R22; R22 is selected from the group consisting of: CrCw alkyl, C2-C1 () alkenyl, C2- C1 () alkynyl, phenyl, _, 95014 -17- 200529810 haloalkyl, alkoxy, thioalkoxy, amine, alkylamino, dialkylamino, carboxyl, alkyl-0C (= 0)-, alkyl-C (= 0)-, aryl-oc (= o)-, alkyl-0C (= 0) NH-, -Oc (= 〇) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (alkyl_〇) r_alkyl, HO_ (alkyl-0 ) r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl_S (= 0) 2-, H〗 NS ( = 0)-and H〗 NS (= 0) 2-; R23 is selected from the group consisting of: Si-Cg alkyl, C2-C6 fluorenyl, C2-C6 alkynyl, F, Cl, Br, I, haloalkane Group, -NH2, -NHR23a, -N (R23a) 2, -N3, -N02, -CN, CNO, -CNS, -C (= 0) OR23a, -C (= 0) R23a, -〇C ( = 0) R23a, -N (R23a) C (= 0) R23a, -C (= 0) N (R23a) 2, ureido, -〇R23a, -SR23a, -SHDKCVQ alkyl), _S (= 〇) 2 · aryl and -S (= 0) 2-N (R23a) 2; 1 ^ 233 is 11 or Ci-Q alkyl; or, two R23a may be merged with the N atom to which they are connected to ® forms a 5- to 7-membered heterocyclic group; and r is 2, 3, 4, 5, 6, 7, 8, 9 or 10; with the proviso that when X is RAC (= 0) _, ra Is a C4-Ci5 straight chain alkyl group substituted with R2O, and R20 is -CN, -C02 Η, -C (= 0) 0-R2 0 a, -NHS (= 0) 2R2 () a, _NHC ( = O) When R20a, -NHR20b or phthalimidine group; then R2 is not-(CH2) aCH2NHC (= NR4) NH-Y, where Y is Η, -CN -N02 or a guanidino protecting group. 58_ Compounds of formula (I) as claimed in claim 1: 95014 • 18- 200529810 Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: "is a cardio-fluorenyl; R2 is-(CH2) a CH2 NHC (= NH) NH-Y,-(CH2) c CH2 NHCONH2 or-(CH2) dCH (R7) NR9R10; a is 1, 2 or 3; c is 1, 2 or 3 d is 0 or 1; R7 is fluorene or methyl; R9 is alkyl; R1 () is fluorene, q-Cw alkyl or amine protecting group; Y is fluorene, CN or N02; Q is -B (OH ) 2, pinanediol dihydroxyborane ester, dicyclohexyl-1, Γ-diol dihydroxyborane ester or 1,2-dicyclohexyl-ethane-1,2-diol dihydroxyborane ester ; X is rac (= o)-, ranhc (= o)-, ras (= o) 2-, raoc (= o)-, rasc (= o)-, or ra; RA is Ci replaced by R2G as appropriate -Cw alkyl; c2-c2G alkenyl optionally substituted by r2G; c2-c2G alkynyl optionally substituted by r2G; carbocyclyl substituted by 1-5 R21 optionally; or 95014 -19- 200529810 as In the case of heterocarbocyclic groups substituted by 1-5 R2 1; R2G is selected from the group consisting of: -CN, i-based, haloalkyl-, Q-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, -co2h, -C (= 0) C02H, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2, -S (= 0) 2NH2, -OH, -SH,- NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHC (= 〇) R2 () a, -NHC (= O) OR20a, -OR2 0 a,- SR2 0 a, -S (= 0) R2 0 a, -S (= 〇) 2 R2 0 a, -s (= 0) 2 -NHR2 0 a, _ -SC (= 0) R2 () a, -C (= 0) R2Ga,- C (= 〇) NHR20a, -C (= O) 〇-R20a, -NHS (= 0) 2R2 () a, -NHR2 () b, phthalimide, and (0-alkyl) r, -0-alkyl-OH,-(0-alkyl) ^-O11, -0112 (). , Name 112 () (:, -0-alkyl-R20c, -S-alkyl-R2Gc, -S (= O) -R20c, -S (= O) 2-R20c, -S (= O) 2- NHR20c, -SC (= O) R20c, -C (= O) R20c, -C (= O) OR20c, -C (= 〇) NHR2Ge, a carbocyclic group substituted with 1-5 R21 as appropriate; and In this case, a heterocarbocyclic group substituted with 1-5 R21; 112 "is (: 1-(: 2 () alkyl, (: 2 (20alkenyl, or (: 2-〇2 () alkynyl); where the Alkyl, Φ alkenyl or alkynyl is optionally substituted by one or more halo, Ci -C4 alkyl, aryl, heteroaryl or -NHR2Gb; R2 () b is an amine protecting group; R2Ge is regarded as Carbocyclic groups substituted by 1 to 5 R22, or heterocarbocyclic groups substituted by 1-5 R22, as appropriate; r21 is selected from the group consisting of: ci-C20 alkyl, C2-C20 alkenyl, C2-C2 〇alkynyl, CVC20 alkoxy, ci_c20 thioalkoxy, -OH-CN, halo, haloalkyl, -NH2, -NH (alkyl), -N (alkyl), -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 0) 0- 95014 -20- 200529810 alkyl, -C (= 0) alkyl, -s (= o) -alkyl , -S (= 0) 2-alkyl '-s (= 0) -aryl, -S (= 0) 2-aryl, optionally hindered by 1-5 R2 2 and optionally Replaced by 1-5 R22 Cyclic group; R22 is selected from the group consisting of: q-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, phenyl, halo, haloalkyl, alkoxy, thioalkoxy, amine, alkylamino , Dialkylamino, carboxyl, alkyl-oc (= o)-, alkyl_c (= 0)-, aryl-oc (= o)-, φ alkyl-0C (= 0) NH- , Aryl-0C (= 0) NH_, alkyl-C (0) NH-, alkyl-C (= 0) 0-, (carbonyl_0) r-carbonyl, HO- (carbonyl-0 ) r _alkyl-, -OH, -SH, -CN, -N3, -CNO, _CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2 NS (= 0 )-And H2 NS (= 0) 2-; and r is 2, 3, 4, or 5; the additional condition is that when X is RAC (= 0)-, RA is a C4-C15 straight-chain substituted by R20 Alkyl and R20 are -CN, -C02H, -C (= O) O-R20a, • NHS (= 〇) 2R2 () a, -NHC (= O) R20a, -NHR20b, or phthalic acid # Imine group; then R2 is not-(CH2) aCH2NHC (= NR4) NH_Y, where γ is Η, -CN or -N02. 59. A compound according to claim 58, wherein R1 is 2-propyl. 60. A compound such as Qing seeking item 58, wherein Q is -B (OH) 2. 61. The compound of item 58, wherein q is a pinanediol dihydroxyborane ester. 62. The compound of item 58, wherein X is rAc (= 〇)-. 63. The compound as claimed in May, wherein R2 is -CH2NH-C (= 0) 0CH2 (C6H5). 64. The compound as claimed in claim 58, wherein X is RAC (= 0)-and RA is CVq 6 alkyl. 95014 200529810 65. The compound of claim 58, wherein χ is rAc (= 0) ·, and rA is an aryl group optionally substituted with 1-3 R2 1. 66. The compound of claim 58, wherein χ is rAc (= 0) ·, and # is a heterocarbocyclic group optionally substituted with 1-3 R2 1. 67. The compound of claim 58, or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R1 is 2-propyl; Q is -b (oh) 2 or pinanediol di Hydroxyborane ester X is RAC (〇)-; and RA is a CVCU alkyl group; an aryl group optionally substituted with a ^^; or a heterocarbocyclic group optionally substituted with 1-3 R2 1. A compound of formula ①: Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R SC "C6 alkyl, C2_c6 diyl, C2_C6 alkynyl or C3_C7 cycloalkyl; R2 is -CH2 NH2 or -CH2 NR9 R1 〇; R9 is fluorene or CVC10 alkyl; R is fluorene, (VCm alkyl, carbocyclyl, heterocarbocyclyl, c alkyl-c (-o &gt;, carbocyclyl_c (= 〇) ·, Heterocarbocyclyl, carbocyclyl ((-〇) ... heterocarbocyclylalkyl-C (= 0)-, qoalkyl-s (= o) 2-, Cyclo-s (= 〇) 2-, Carbocycloalkyl95014-22-200529810 Name (= 〇) 2-, Heterocarbocycloalkyl Name (= 〇) Plant, Cl_Cl () alkyl-NHC ( = 0)-, carbocyclyl-NHC (= 〇) ... heterocarbocyclyl_NHC (= 〇) _, carbocyclylalkyl-NHC (= 0)-, heterocarbocyclylalkyl_NHC (= 〇) _, Ci_c⑶ Yuan-0C (= 0) _, carbocyclyl_〇c (== 〇) _, heterocarbocyclyl-〇c (= 〇) _, carbocyclyl-0C (= 0)-, heterocarbocycloalkyl_oc (= 〇)-or amine-protecting group; wherein R10 is optionally substituted by 1, 2 or 3 R2 3; or 'R9 is connected to R1G and their N atoms together form a heterocarbocyclic group; φ Q is seven (0H) 2, _B (0Rl 4) 2 or a cyclic dihydroxyborane Ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms and optionally a hetero atom which can be N, S or 0; R14 is fluorene, CrQ alkyl, cycloalkyl, cycloalkyl Alkyl, aryl or aralkyl; X is RAC (= 0)-, ranhc (= o)-, ras (= o) 2-, raoc (= o)-, rasc (= o &gt; or Ra; RA Ci-Qo alkyl substituted by r2G as appropriate; R2 optionally substituted by C〗 -C〗 ο dilute group; Yi ^ C2 -C substituted by R2 G if appropriate 快 fast group, optionally 1 -5 carbocyclic groups substituted with R21; or • heterocarbocyclic groups optionally substituted with 1-5 R21; R2 () is selected from the group consisting of: -CN, halo, ii, and C! -C4 Alkyl, C2-C4 dilute, C2-C4 alkynyl, &lt; 302Η, -c (o) co2h, -C (= 0) NH2, -C (= 0) H, -S (= 0) NH2 , -S (= 0) 2NH2, -OH, -SH, _NH2, -NH (alkyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHCK &gt;) H2 () a '- NHCH)) OIl2 () a, 95014 -23- 200529810 -OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= Q) 2 -NHR2 0 a, _SC (= O) R20a, -C (= O) R20a, -C (= O) NHR20a, _C (= O) O-R20a, -NHS (= O) 2R20a, -NHR20b, neighbor Benzodiazepine Group,-(〇alkyl) r, -0_alkyl-OH,-(0 · alkyl) r-OH, -OR2Gc, -SR2 () C, -0-alkyl-R2Ge, each alkyl group- R2Gc, -S (= 0) -R2 () c, -S (= O) 2-R20c, -S (= O) 2-NHR20c, -SC (= O) R20c, -C (= O) R20c, -C (= O) OR20c, _C (= 0) NHR2Ge, a carbocyclic group substituted with 1-5 R21 as appropriate; and a heterocarbocyclic group substituted with 1-5 R21 as φ; alkyl, C2 -C20 alkenyl or C2_C20 alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally substituted with one or more halo, alkyl, aryl, heteroaryl or -NHR2Gb; &amp; 2 () 15 Is an amine protecting group; R2Ge is a carbocyclic group optionally substituted with 1-5 R22; or a heterocarbocyclic group optionally substituted with 1-5 R22; R21 is selected from the group consisting of: Lu C! -C2. Alkyl, C2-C2oalkenyl, C2-C2oalkynyl, Ci-C2oalkynyl, Ci-C2Q thioalkoxy, -OH-CN, _yl, 12-alkyl, -NH, &quot; NH (alkyl), -N (alkyl), -NHC (= 0) 0-alkyl, -NHC (= 0) alkyl, -C (= 〇) 〇-alkyl, -C (= 0) Carbonyl, -S (= 0) -Carbonyl, -S (= 0) 2 -Carbonyl, -S (= 0) ** Aryl, -S (= 0) 2-Aryl, as appropriate Carbocyclyl substituted with 1-5 R22 In addition, heterocarbocyclic groups substituted by 1-5 R22; R22 is selected from the group consisting of: CVCh alkyl, C2-C1G alkenyl, C2-C1G alkynyl, phenyl, alkynyl, haloalkyl, alkoxy, Thioalkyl, amine, amine, diamine 95014 -24- 200529810, carboxyl, alkyl-OC (= 0)-, alkyl-C (K))-, aryl-oc ( = o)-, alkyl-OC (= 0) NH-, aryl-0C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (Alkyl-〇) r-alkyl, HO- (alkyl-0) r-alkyl-, -OH, -SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0 )-, Alkyl-S (= 0) 2-, H2NS (= 0)-, and H2NS (= 0) 2-; R23 is selected from the group consisting of: CrC6 alkyl, C2-C6 alkenyl, (: 2_ (: 6 alkynyl, F, Cl, Br, I, Haloalkyl, -NH2, -NHR23a, -N (R23a) 2, · N3, -N02, -CN, -CNO, -CNS, _C (= 0) 0R23a, -C (= 0) R23a, -0C ( = 0) R23a, -N (R23a) C (= 0) R23a, _c (= 0) N (R23a) 2, ureido, -OR23a, _SR23a, 4 (= 0) 2 ^ (6 alkyl),- S (= 0) 2_ aryl and -S (= 〇) 2_N (R23a) 2; Chi 23 &quot; is ^ [or CrC6 alkyl; Alternatively, 'two R23a may be combined with the N atom to which they are attached to form a 5- to 7-membered heterocyclic group; and 42, 3, 4 or 5. Nu Ming seeking compound of item 68, wherein Ri is 2-propyl. Nu Ming seeking compound of term 68, wherein q is _b (〇h) 2. S 'is, for example, a compound of the term 68, wherein Q is a pinanediol dihydroxyborane ester. A compound in which the term 68 was found in July, where χ is rAc (= 〇) _. : A compound of item 68, wherein R2 is heptamin NH-C (= 〇) 〇CH2 (q%). A compound of moon term 68, wherein χ is rac (= 0) _ and rA is an alkyl group. 4 16 75 · A compound of the same formula as in item 68 where X is RA c (= o) · ′ and RA is optionally 95014 -25- 200529810 aryl group substituted with 1-3 R2 1 76. The compound of claim 68, wherein 乂 is # 〇 (= 〇) ... and # is a heterocarbocyclic group optionally substituted with 1-3 R2 1. 77. The compound of claim 68, or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: 〃 R1 is 2-propyl; Q is pinanediol dihydroxyborane; X RAC (K))-; and RA is a C4-C10 alkyl group; an aryl group optionally substituted with 1-3 ^ 1; or a heterocarbocyclic group substituted with 1-3 R2 1 as appropriate. 78. A compound having the formula ① as claimed in claim 1: Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R is &lt; ^-(: 8 alkyl, c2-c8 alkenyl, c2-c8 alkynyl, or c3-c7 cycloalkyl ; R2 is H; Q is -b (〇h) 2, _b (orm) 2 or cyclic dihydroxyborane ester, wherein the cyclic dihydroxyborane ester contains 2 to 20 carbon atoms, and optionally contains One heteroatom which may be N, S or 0; R is Η, C ^ C: 4 alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; X RAC (= 〇) _, raNHC (= 0)., RAS (= 0) 2. RA0c (= 〇)-. rASC (= 0)-95014 -26- 200529810 or RA; RA is CVQo alkyl substituted by R2G as appropriate; C2-C2 () alkenyl substituted with R2G as appropriate; C2-C2G alkynyl substituted with R2G as appropriate; carbocyclyl substituted with 1-5 R22 as appropriate; or 1-5 R22 as appropriate Heterocarbocyclyl; R2G is selected from the group consisting of: -OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= 0) 2 -NHR2 0 a, SC (= O) R20a, -C (= O) R20a, -C (= O) NHR20a, _C (= O) O-R20a, o-phenylenediimide,-(〇-alkyl) r, -O-alkyl-OH ,-(0-alkyl) r-OH, -OR20c, -SR20c, -0-alkyl-R20c, alkyl-R20c, -S (= 〇) -R20c, -S (= O) 2-R20c, -S (= O) 2-NHR20c, -SC (= O) R20c, -C (= 〇) R2〇c, -C (= O) OR20c, -C (= O) NHR20c. R22 substituted carbocyclyl groups; and optionally 1-5 R22 substituted carbocyclyl groups; R is C! -C2o alkyl, C2-C2o diradical or C2-C2o fast group; wherein the Alkenyl, alkenyl or alkynyl are optionally substituted by one or more i, alkyl, aryl, heteroaryl or -NHR2Gb; R2Ge is a carbocyclic group optionally substituted by 1-5 R22; or Heterocarbocyclic groups substituted by 1-5 R22 as appropriate; R is selected from the group consisting of: Ci_C10 alkyl, C2-C10 alkenyl, C2_C10 alkynyl, phenyl, halo, alkyl, oxy, sulfur Oxy, amine, amine, diamine, carboxyl, alkyl-OC (= 0)-, alkyl-C (= 0)-, aryl-oc (= 〇)-, 95014 -27- 200529810 alkyl -0C (= 0) NH-, aryl- ° C (= 0) NH-, alkyl-C (= 0) NH-, alkyl-C (= 〇) 〇-, (alkyl-〇) r -Alkyl, ΗΟ- (alkyl-〇) r-alkyl-, -OH, SH, -CN, -N3, -CNO, -CNS, alkyl-S (= 0)-, alkyl-S (= 0) 2-, H2NS (= 0)-, and H2NS (= 0) 2-; and Γ is 2, 3, 4, 5, 6, 7, 8, 9, or 10. 79. The compound of claim 78, wherein: X is RAC (= 〇)-, RANHC (= 0)-, RAS (= 0) 2-, or RA; RA is Ci-Cw alkyl substituted with R20 as appropriate R2G is alkyl,-(0-alkyl) r, -0alkyl-oh or-(〇alkyl) r-OH; and r is 2, 3, 4 or 5. 80. A compound according to claim 78, wherein the 0-alkyl is methoxy, ethoxy or propoxy. 81.-A compound of formula (1) as claimed in claim 1: Or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein: R is 2-propyl; r2 is -ch2ch2ch2nhc (= nh) nh-no2, -ch2ch2ch2nhc (= o) nh2, -ch ( ch3) oh, -ch2conh2, -ch2nh24-ch2nr9r10 R9 is Η; Rl 0 is fluorenyl_c (= o) _, ethyl-C (= 0)-, propyl-c (= o)-, butyl -c (= o)-, pentyl-C (= 0)-, 2- (ethoxycarbonyl) ethyl-C (= 0)-, 4-methyl-phenyl 95014 -28- 200529810 -C (= 0)-, cyclopropyl-c (= 0)-, 4-fluorophenyl-CH))-, 4-H2NS02-phenyl-C (= 0)-, 4-H3 CS02 -benzene -C (K))-, 4-phenyl-phenyl-C (= 0)-, 3,4-dimethoxy-benzyl-c (= 0)-, 3-pyridyl-C ( = 0)-, 2- (Cycloyl) than hydradin-3-yl-C (= 0)-, 6- (morpholinyl) -p ratio σ-determin-3-yl-C (= 0)- , 2- (pyridin-4-yl) thiazolyl-C (= 0)-, 2-pyridyl-C (= 0)-, 2,5-dimethyl-pyrazolyl-C (= 0 )-, N-methyl-2-pyrrolyl-C (= 0)-, 2-tetrahydro p-specific groups -C (= 0)-, 2-thiophenyl-C (= 0)-, 5-isolipid σ sitting group -C (= 0)-, 4- (tetramethyl-5-yl) phenyl-C (= 0)-, (5-four mouth sitting group) ch2-c (= o ) _, N_h3cso2_ hexahydropyridyl_c (= o) _, butyl-0C (= 0)-, (benzyl) -0C (= 0)-, (9-thylmethyl) -0C (= 0)-, pentyl-NHC (= 0)-, propyl-NHC (= 0)-, phenyl-NHC (= 0)-, 4-methyl-phenyl-NHC (O)-, methyl -S (= 0) 2-, 4-fluorophenyl-S (= 0) 2-, 4-cyano-phenyl-S (= 0) 2-, 1-methyl-imidazol-4-yl-S (= 0) 2-, 2-thiophenyl-S (= 0) 2-, (4-methyl-phenyl) -NHC (= 0) NH-S (= 0) 2-and (4-methyl -Phenyl) -S (= 〇) 2NHC (= 0)-Alternatively, R9 forms a pyrrole together with R1g and the N atom to which they are attached Or pyrazolyl; Q is -b (oh) 2, pinanediol dihydroxyborane ester, dicyclohexyl-U'-diol dihydroxyborane ester, or 1,2-dicyclohexyl-ethane-1 , 2-diol dihydroxy boron ester; X is rac (= o)-, ranhc (= o)-, ras (= o) 2-, or raoc (= o)-; anti-eight is CH3-, C2H5- , C3H7-, C4H9-, C5Hn-, C6H13-, C7H15-, C8H17-, C9H19-, C10H21-, CnHw, C12H25-, C13H27-, Gold Steel Alkenyl-, Bicycloheptyl-, 95014 200529810 was replaced by r2G C3 alkyl; c2_1G alkenyl substituted by r2G; cyclopropyl substituted by 0-3 R2 1; cyclopentyl substituted by 0-2 R21; ring substituted by 0-2 R2 1 Hexyl; phenyl substituted with 0-3 R2 1; fluorenyl substituted with 0-2 R21; pyrigyl substituted with 0-1 R21; φ quinolinyl substituted with 0-1 R21; Imidazolyl substituted with 0-1 R2 1; Tetrahydrofuranyl substituted with 0-1 R2 1; Ketopyrazolidinyl substituted with 0-1 R21; Benzopyrazolyl; pyrazolyl substituted with 0-2 R2 1; furyl substituted with 0-2 R2 1; tetrahydropyrrolyl substituted with 0-1 R21; spring Hexahydropyridyl substituted with 0-1 R21; hexahydropyridyl substituted with 0-1 R2 1; or σ-substituted with 0-1 R21; R2G is selected from the group consisting of: hydroxy-, methyl Oxy-, ethoxy, propoxy-, butoxy-, pentoxy-, hexyloxy-, heptyloxy-, octyloxy-, ethoxyethoxy, ethoxyethoxy Ethoxy, methyl-S-, ethyl-S-, octyl-S-, fluorenyl-C (= 0) S-, (ethylamido) methyl-S-, amine-, Fluorenylamino-, 95014 -30- 200529810 dimethylamino-, methyl-c (= o)-, phenyl-c (= o)-, (h3 cso2) phenyl-c (= o)-, Ishihara phenyl-c (= o)-, methyl_oc (= o), ethyl_oc (= o) _, butyl-0C (= 0) NH-, methyl-C (= 0 ) NH-, methoxyethoxymethyl-C (= 0) NH-, H2NC (= 0)-, methyl_NHC (= 0) _, ethyl-NHC (= 0)-, propyl -NHC (= 0)-, phenyl-NHC (= 0)-, H2NC (= 0) NH-, H2NS (= 0) 2-, octyl-s (= o) 2-, phenyl-s ( = o) 2-, Methylphenyl-S (= 0) 2-, Ishihara phenyl-S (= 〇) 2-, Pyridyl-, badhexyl-, badheptyl-based, Jingang Methyl-, dicycloheptyl-, cyclopentenyl-, phenyl-, methoxy-phenyl-, methyl-phenyl-, di -Phenyl-, ethyl-phenyl-, propyl-phenyl-, butyl-phenyl-, fluorophenyl-, difluoro-phenyl-, p-phenyl-, &gt; , Mothyl-, dimethylamino-phenyl-, oxalyloxy-, 2-isopropyl-5-methyl-¾hexyloxy-, naphthyl-, methoxyfluorenyl-, Methoxy-, phenoxy-, (methyl-phenyl) oxy-, (ethyl-phenyl) oxy-, (propyl-phenyl) oxy-, (butyl-phenyl) Oxy-, (fluorophenyl) oxy-, (chlorophenyl) oxy-, (bromophenyl) oxy-, φfluorenyl-S-, fluorenyl-S-, (methyl · phenyl ) Methyl-S-, Pyrimidinyl-S-, Hexamidine-stilbyl-, N-Methyl-Hexazolidine-stilbyl-, n-propyl-Hexamidine-pyridyl-, phthalate Fluorenimine-, thiophenyl-, methyl-thiophenyl-, miso-, olanyl-, tetrasigma group, 8¾-tetrahydropyrrolyl-, indolyl-, and Fluorenyl, indolyl-; and R21 are selected from the group consisting of: methyl-, ethyl-, propyl-, butyl-, pentyl-, hexyl-, heptyl-, ethyl fine-, propyl fine- , Butyl-, methoxy-, ethoxy, propoxy-, phenoxy-, fluorine-, chlorine- Bromine -, methyl -C (= 0) -, 95014 -31 - 200529810 Butyl-0C (= 0)-, Butyl-0C (= 0) NH-, Phenyl-, Methoxyphenyl-, Phenyl-, Phenyl-, &gt; Styrenyl-, P Ratio Rocky- and P ratio σ-fixed-. 82. A compound selected from: Example number Compound name D.1.1 D-2 · carboxamide, 怍 [(13) _1-[[[(11〇 小 [(3 &amp;3,43,63; ^ 1) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] Amine radical PK [imine (acylamino) methyl] amino] butyl] D.1.2 2-pyridoxinecarboxamide, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborofluorene-2- [Methyl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (Amino) methyl] amino] butyl]-D.1.3 3- (1,3- Di-yl-1,3-dihydro-iso ^ budol-2-yl) -propanamide, N-[(1S) -1-[[[(1R) 小 [(3 &amp; 3,48,68 , 7 &amp; 11) -hexahydro-3'5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane [Amino] Amino] carbonyl] -4-[[Imine (alkylamino) methyl] amino] butyl] D.1.4 4-Butylbenzylamine, N-[(lS) -1 -[[[(lR) _l _ [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine Nitroamino) methyl] amino] butyl] D.1.5 3-[(1,1-Difluorenylethoxy) carbonylamino] benzamidine, [[13) -1- [ [[(111) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp; 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxyborin-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl]-D.1.6 2 -(2-methoxyethoxy) acetamidamine, 仏 [(13) -1 _ [[[(111) 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ( Tylamino) methyl] amino] butyl D.1.7 2- [2- (2-methoxyoxyethoxy) ethoxy] acetamidamine, N-[(lS) -l-[[ [(lR) -l-[(3aS, 4S, 6S, 7aR) -AlL-3a, 5,5-STS -4,6-methylalanyl-1,3,2_phenylhydrazine dioxinol- 2-yl] -3-methylbutyl] amino] chinyl] -4-[[imine (tylamino) methyl] amino] butyl95014 -32- 200529810 D.1.8 (E) -3- (Ethoxycarbonyl) propenamide, 1 ^ [(13) small [[[(111) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxoamido-2-yl] -3_methylbutyl] amino] guito] -4-[[亚Amine (Sulmonylamino) methyl] amino] butyl] D.1.9 2-Hexahydropyridyl-acetamidoamine, [[13) -1-[[[(111) -1- [ (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxo-2-yl] -3- Methylbutyl] amino] carbonyl] -4-[[iminoamidoamino] methyl] amino] butyl] D.1.10 4- (1-methyl-hexahydropyridin-4-yl ) Butamidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4, 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[iminofluorenylamino) methyl [Amino] amino] butyl] D.1.11 2-Ethylamido-acetamidoamine, N-[(lS) -1-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -Hexaaza-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino ] Carboxy] -4-[[Imino (methylamino) methyl] amino] butyl] D.2 .1 4- (methoxycarbonyl) butanidine, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexaaza-3a, 5, 5 -Trimethyl-4,6-methylalanyl-1,3,2-benzodioxocarboxan-2-yl] -3_methylbutyl] amino] several groups] -4-[[ Imidinofluorenylamino) Methyl] amino] butyl] D.2.2 4- (1-Butyl-hexahydropyridin-4-yl) -butanidine, N-[(1S) -1- [[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Shefbonyl-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[iminofluorenylamino) methyl] amino] butyl] D.2.3 2-butyl Oxyacetamidamine, N-[(lS) -l _ [[[(lR) -1-[(3aS, 4S, 6S, 7aR &gt; · Hexa-3-3,5,5-trimethyl-4,6 -Methylalkyl · 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl PK [imino (nitroamino) fluorenyl] amino] Butyl] D.3.1 Decylamine, N _ [(1S) -H [[(1R) small [(3 &amp; 3,43,68,7 &amp;! 〇-hexahydro-3'5,5-trisyl 4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] aminoyl] ice [[imine (amidylamino) Methyl] amino] butyl] 95014 -33- 200529810 D.3.2 Naphthalene small carboxamide, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] guito] -4-[[imino (Nitroamino) methyl] amino] butyl] D.3.3 2-phenylacetamidamine, 1 ^-[(13) small [[[[(1 扣 -1-[(3 &amp; 8,43 , 63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] _3-methyl Butyl] amino] weiyl] -4-[[imine (canylamino) methyl] amino] butyl] D.3.4 1-phenylcyclopentanecarboxamide, swimming [(18 ) -1 _ [[[((111) _1-[(3 &amp; 8,48,68,7 &amp; feet) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methanyl-1, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl] amino] butyl Group] D.3.5 (2R) -2-phenylbutamidamine, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) · six-rat-3a , 5,5-Dimethyl-4,6-methylalkynyl-1,3,2_benzodioxolium-2-yl] _3_methylbutyl] amino] jiki] -4- [[Imine (nitroamino) methyl] amino] butyl] D.3.6 (2S) -2-phenylbutanamide, N- [ (1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-dimethyl-4,6-methylalkyl-1,3,2- Benzodioxol-2-yl] -3-methylbutyl] amino group] -4 _ [[Imine (acylamino) methyl] amino] butyl] D.3.7 Dodecylamine, 1 ^ [(13) 小 [[[(111) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4, 6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] Jinyl] ice [[Imine (pyridylamino) methyl Yl] amino] butyl] D.3.8 Octylamine, N-[(1S) small [[[((11〇-1 _ [(333,48,63,7 &amp; 11) -hexahydro-315,5- Trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (Nitroamino) methyl] amino] butyl] D.3.9 Acetylamine, N _ [(1S) -1-[[[(1R) 小 [(3 &amp; 8,48,63,7 &amp; 1〇-hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2 · benzodioxofluoren-2-yl] -3-methylbutyl ] Amino organic hydrazone-[[Imine (acylamino) fluorenyl] amino] butyl] 95014 -34- 200529810 D.3.10 4- (1,1-Dimethylethyl) cyclohexanecarboxamide, N-[(1S) -1-[[[((lR) _; l · [(3 &amp; 3,43,63 , 7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.11 trans-4-pentylcyclohexanecarboxamide, N_ [ (1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3, 2-benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[iminoamidoamino) methyl] amino] butyl] D .3.12 4-phenylbutyramide, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43,63,7 &amp; 11) _hexahydro-3a, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-amidinobutyl] amino] yiyl] -4-[[imino (Nitroamino) fluorenyl] amino] butyl] D.3.13 2- (3-methoxyphenyl) acetamidamine, [(18) -1-[[[(1foot) -1_ [( 3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxolane-2-yl] -3-form Butyl] amino] carbonyl] -4-[[iminoamidoamino) methyl] amino] butyl Group] D.3.14 4- (1,1-Dimethylethyl) benzamide, N-[(1S) -1-[[[((1R) -1-[(3 &amp; 3,48,68 , 7 &amp; 1〇_hexahydro-3 &amp;, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl] amino] carbonyl] ice [[imine (alkylamino) methyl] amino] butyl] D.3.15 nonamidine, N _ [(1S) small [[[(111) 小 [ (3 &amp; 8,48,68,7 &amp; 11) _Hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2 -Yl] -3-methylbutyl] amino] carbonyl; HK [imine (tylamino) methyl] amino] butyl] D.3.16 (RS) -2-cyclopentylhexyl Amine, N-[(1S) -1 _ [[[(1R) -1_ [(3 &amp; 3,48,68々11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methane -1,3,2-benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] Amine] butyl] D.3.17 Pyridin-2-carboxamide, 怵 [(18) -1 _ [[[(11〇-1-[(3 &amp; 3,43,63,7 &amp; 11) -six Hydrogen-3a, 5,5-trimethyl · 4,6 · fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] several Yl] ice [[imino (nitroamino) methyl] amino] butyl] 95014 -35- 200529810 D.3.18 2,3-difluorobenzamide, N _ [(1S) -1-[[[((1R) 小 [(3aS, 4S, 6S, 7aR) 4 mouse-3a, 5,5_dimethylformamide -4,6-methylalanyl-1,3,2-phenylfluorenyldioxo-2-methyl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Methylamino) methyl] amino] butyl] D.3.19 2- (2-iodophenyl) acetamidamine, N-[(1S) -1-[[[((1R) small [(3aS, 4S , 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 · methylbutane [Amino] Amino] Jinyl] -4-[[Imine (songylamino) methyl] amino] butyl D.3.20 cyclohexanecarboxamide, N-[(1S) -1- [ [[(IR) 小 [(3 &amp; 3,43,63,7 &amp; H) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxyborin-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.21 2- (4-Bromophenyl) acetamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ( Nitroamino) methyl] amino] butyl] D.3.22 benzamidine, N-[(1S) small [[[(11〇 Small [(3 &amp; 8,48,68,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl · 1,3,2-benzodioxoborohydride- 2-yl] -3-methylbutyl] amino] quinyl] -4-[[imino (triamino) methyl] amino] butyl] D.3.23 2-methylbenzyl Hydrazine, N-[(lS) -l-[[[(lR) -1-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trifluorenyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] Amine] butyl] D.3.24 4-bromobenzylamine, N-[(lS) -1-[[[(lR) -l _ [(3aS, 4S, 6S, 7aR) _A hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] quinyl] -4- [[Imine (acylamino) methyl] amino] butyl] D.3.25 (2S) -2-phenylpropanamide, N-[(1S) -1-[[[(1R) Small [(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trimethyl_4,6-methylalkyl-1,3,2_benzodioxofluoren-2-yl]- 3-fluorenylbutyl] amino] weiyl] -4-[[iminofluorenylamino) fluorenyl] amino] butyl] 95014 -36- 200529810 D.3.26 (Ee) -2-methyl-3-phenyl-acrylamidine, 1 ^-[(18) -1-[[[(1foot) -1-[(3 &amp; 3,43,63 , 7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3-methylbutyl] Amine radical] _4 _ [[Imine (nitroamino) methyl] amino] butyl] D.3.27 2-[(naphthyl-2-yl) oxy] acetamidine, N-[( 1S) -H [[(1R) -1-[(3 &amp; 3,43,63,7 &amp; 1〇-hexahydro-3 \ 5,5-trimethyl-4,6_methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] each methylbutyl] amino] kisyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.28 2,2-Dimethylbutyramide, N-[(lS) -H [[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethylamine -4,6-methylalkyl_1,3,2_benzodioxofluoren-2-yl] each methylbutyl] amino group] -4-[[imino group ) Methyl] amino] butyl] D.3.29 2 · (2-chlorophenyl) acetamidamine, N-[(lS) -1-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -Hexa-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxocarbox-2-yl] -3-fluorenylbutan [Amino] Amino] Jinyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.3.30 5-methylpyridine- 2-carboxamide, hydrazone [(18) 小 [[[(1 幻 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4, 6-Methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] several groups] -4-[[imino (nitroamino ) Methyl] amino] butyl] D.3.31 cis-3- (2-methoxyphenyl) acrylamidonium, N-[(1S) small [[[((1R) -1_ [(3 &amp; 3 , 43,68 &gt; 11) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane-2-yl] -3- Methylbutyl] amino] kisyl] ice [[imino (trimethylamino) methyl] amino] butyl] D.3.32 (2-methylphenoxy) acetamidine, hydrazone [ (13) small [[[((111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro_3 \ 5,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxon-2-yl] -3-methylbutyl] amino]] [[imino (linylamino) methyl] amino] butyl] D.3.33 2- (2,5-dimethylphenyl) acetamidamine, [(18) -1-[[[(11〇 小 [(3 &amp; 3,43,63,7 &amp; ^ &gt; Hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylfluorenyl dilactam-2-yl] -3-methylbutyl] amino] Group] -4-[[imino (nitroamino) methyl] amino] butyl] 95014 -3 7- 200529810 D.3.34 trans-3- (2-bromophenyl) acrylamide, [[13) -1-[[[(11〇-1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxolyl-2-yl] -3-methylbutyl] amino] carbonyl ] _4 _ [[Iminoiminoamido) methyl] amino] butyl] D.3.35 4-isopropylbenzamide, N-[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl · 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] _3 _Methylbutyl] amino] weiyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.36 4- (4-methylphenyl) butanamide , N-[(1S) -H [[(1R) -1-[(3 &amp; 3,43,68,7 &amp; 1〇-hexahydro-3 &amp;, 5,5-trimethyl-4,6- Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl ] Amino] butyl] D.3.37 2- (2-fluorenylthio) acetamidine, N _ [(1S) -1 _ [[[(1R) -1_ [(3 &amp; 3,43,68,7 & amp 11) -hexahydro-3'5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] -4-[[Imine (Zoylamino) methyl] amino] butyl ] D.3.38 5-methylhexamidine, [[18) -1-[[[(111) -1-[(338,43,63; ^ 10-hexahydro • 3a, 5,5_ Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] _3_methylbutyl] amino] several groups] ice [[imino Methylamino) methyl] amino] butyl] D.3.39 3-pyrimidin-2-yl-propanamidin, N-[(1S) small [[[((lR) -H (3aS, 4S, 6S , 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amino group] -4 · [[Imine (nitroamino) methyl] amino] butyl] D.3.40 2,4-Dimethylpyrazole-5-carboxamidin, [ (18) Small [[((111) Small ((3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3'5,5_trimethyl-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.41 Furan-3-carboxamide, N-[(1S) -1 _ [[[((1R) 小 [(3 &amp; 3,48,63,7 &amp; 11) -hexahydro-3a, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl group; | winter [[imine group ( Nitroamino) fluorenyl] amino] butyl] 95014 -38- 200529810 D.3.42 (2R) -2-phenylpropanamide, N-[(lS) _l-[[[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4-[[imine (Nitroamino) methyl] amino] butyl] D.3.43 2-cycloheptylacetamidamine, N-[(lS) -1-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] _3-methylbutane [Amino] amino] Weiyl] -4-[[Imine (acylamino) methyl] amino] butyl] D.3.44 1-methylcyclopropanecarboxamide, N-[(1S) -1-[[[((1R) -1_ [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2 · benzene Benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (trimethylamino) methyl] amino] butyl] D.3.45 1-methyl-cyclohexanecarboxamide, 仏 [(18) -1-[[[(11〇 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino Amino) methyl] amino] butyl] D.3.46 2-[(lS, 2R, 5S) -2-isopropyl- 5-methylcyclohexyl] oxyacetamidamine, [(13) 小 [[[((111) -1-[(338,48,63,7 &amp; 11) -hexahydro-3〇trisyl- 4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] fluorenyl] -4-[[imino (nitrate Methylamino) methyl] amino] butyl] D.3.47 (E) -2-Butenamidamine, N-[(1S) -1-[[[((1R) -1-[(3 &amp; 3 , 43,63 &gt; 10-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methyl group Butyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.48 3-methylbutyramine, ^ 4 (13) small [[ [(111) 小 [(338,43,68,7 &amp; 11) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalanyl-1,3,2-benzodioxane Oxen-2-yl] -3-fluorenylbutyl] aminoyl] -4-[[imine (nitroamino) fluorenyl] amino] butyl] D.3.49 3-phenyl Propylamine, N-[(1S) small [[[(1 幻 小 [(3 &amp; 8,43,68,7 &amp; 10-hexahydro • 3a, 5,5-trimethyl • 4,6- Methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino group; ΗΚ [imino (sonylamino) fluorenyl] amino ] Butyl] 95014 -39- 200529810 D.3.50 4- (4 · methoxyphenyl) -butylamidine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl; HK [ Imino (pyridylamino) methyl] amino] butyl] D.3.51 pyrimidine-3-carboxamide, 仏 [(13) 小 [[[(1 幻 小 [(3 &amp; 3,43 , 68,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-form Butyl] amino] carbonyl] -4-[[imino (trimethylamino) methyl] amino] butyl] D.3.52 2-, sphen-3-yl-acetamidamine, N -[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[iminoamidoamino] methyl] amino] butyl D.3.53 (E) -Pentam-2,4-dienoic acid amide, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro _3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl]- 4 _ [[Imine (acylamino) methyl] amino] butyl] D.3.54 2- (4-isopropylphenoxy Acetylamine, 乂 [(13) 小 [[((111) 小 [(3 汪 8,43,63,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trisyl-4,6_ Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] several groups H-[[imino (nitroamino) methyl] Amine] butyl] D.3.55 2- (4-ethylphenoxy) acetamidamine: ^ [(13) 小 [[[(111) 小 [(3 &amp; 8,48,68,7 &amp; 1 ^)-hexaki-33,5,5-dimethyl-4,6_fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl ] Amine] Hino [H-[[Imine (songylamino) methyl] amino] butyl] D.3.56 (E) -2-methylhex-2-enoic acid amine, N- [(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (trimethylamino) methyl] amino] butyl ] D.3.57 3- (3-methylphenyl) acrylamide, meaning [(18) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) _hexahydro-3a , 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4 -[[Imine (nitroamino) methyl] amino] butyl] 95014 -40- 200529810 D.3. 58 2-adamantane-1-ylacetamidamine, [[13) -1-[[[((11〇_1 · [(3 &amp; 8,43,68,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4 -[[Imine (nitroamino) methyl] amino] butyl] D.3.59 (RS) -2-Cyclopent-2-enylacetamidamine, 沣 [(18) 小 [[[ (11〇-1-[(3 &amp; 8,43,63,7 &amp; 11) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl_1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] ice [[imine (wallylamino) methyl] amino] butyl D.3.60 4-diethylamine Benzamidine, 1 ^ [(13) small [[[(111) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl -1,3,2-benzodioxofluoren-2-yl] _3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino ] Butyl] D.3.61 (RS) -2-Methylbutyramide, N-[(lS) -l-[[[(lR) -l _ [(3aS, 4S, 6S, 7aR) _ hexahydro- 3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino group] H- [[Imine (nitroamino) fluorenyl] amino] butyl] D.3.62 3- (4-fluorenyl Acrylamide, meaning [(18) -1 _ [[[(111) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro_3 &amp;, 5,5-trimethyl-4 , 6-Methylalkyl-1,3,2-benzodilactite pentamidine-2-yl] _3_methylbutyl] amino] kisyl] -4-[[Imine (nitroamino) Methyl] amino] butyl] D.3.63 hexamethylene-2,4-dienoate, N-[(lS) -1-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine []]] [Jinyl] -4-[[Imine (Shistylenylamino) fluorenyl] amino] butyl] D.3.64 4-pyrrole small benzamidine, ^-[(13) -1_ [ [[(111) 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxine -2-yl] -3-methylbutyl] amino] carbonyl] winter [[imine (acylamino) methyl] amino] butyl] D.3.65 (E) -3-fluorene -3-yl-propenamide, hydrazone [(18) small [[[(11〇 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6- Methylalkyl_1,3,2-benzodioxolan-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl ] Amino] butyl] 95014 -41-2005 29810 D.3.66 hept-2-enamine, 1 ^ [(13) -1-[[[(111) -1-[(3 &amp; 3,48,63 &gt; 11) -hexahydro-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4-[[imine (Acylamino) methyl] amino] butyl] D.3.67 2- (3,4-Difluorenylphenoxy) acetamidamine, [[13] -1-[[[(1 Magic-1-[(3 &amp; 3,48,68,7 &amp; 10-hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline -2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.68 decamenylamine, N-[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-dimethyl-4,6-methylalkyl-1, 3,2-Benzamidinedioxolium-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[Imininofluorenylamino) methyl] amino] butyl ] D.3.69 (E) _Undec-2-enoic acid amide, N-[(lS) _l _ [[[(lR) -l-[(3aS, 4S, 6S, 7aR) · Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4- [ [Imino (sonylamino) fluorenyl] amino] butyl] D.3.70 (E) -Dec-3-enoic acid ammonium, N-[(1S ) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2- Benzodioxo-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (sonylamino) methyl] amino] butyl] D .3.71 2,2-dimethyl-3- (2-methylpropenyl) -cyclopropanecarboxamide, N-[(1S) -1-[[[(1R) small [(3aS, 4S, 6S , 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.3.72 2-methylcyclohexanecarboxamide, 1 ^ [(18) -1 -[[[(11〇 小 [(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy Shed oxen-2-yl] -3-methylbutyl] amino] kisyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.73 5- Cyclohexylpentamidine, N _ [(lS) -l-[[[((lR) -1-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5_trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino group] Jinyl] -4-[[Imine group (alkylamino group) Methyl] amino] butyl] 95014 -42- 200529810 D.3.74 3-methoxycyclohexanecarboxamide, 乂 [(18) -1-[[[(111) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp; , 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxy pendant-2-yl] -3-methylbutyl] amino] jiki] -4 -[[Imine (nitroamino) methyl] amino] butyl] D.3.75 (3R) -3,7-dimethyl-oct-6-enoic acid amine, 1 ^-[( 13) -1-[[[((11〇-1-[(3 &amp; 8,48,68,7 &amp; 1 ^)-hexaki-3 &amp;, 5,5-dimethyl-4,6-methane Benzene-1,3,2-benzo-dibenzofuran-2-yl] -3-methylbutyl] amino] several groups] -4-[[imino (nitroamino) a Group] amino] butyl D.3.76 3-[(4-methylbenzyl) thio] propanilamine, N-[(1S) -1-[[[((1R) -1-[(3 &amp; 8, 43,68,7 &amp; 11) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxin-2-yl] -3 -Methylbutyl] amino] chino] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.77 (3S) _3,7-dimethyloctyl- 6-enoic acid ammonium amine [(18) small [[[(11〇-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6 · Methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] several groups] -4-[[imino (nitro Methyl) amino] butyl] D.3.78 (RS) -4-ethyloctylamine, N-[(1S) -1 _ [[((1R) small [(3aS, 4S, 6S, 7aR ) -Hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine Phenyl] carbonyl] -4 · [[imino (reminylamino) methyl] amino] butyl] D.3.79 5-fluoro-2-methoxybenzamide, N-[(1S ) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 · trimethyl-4,6-methylalkyl-1,3,2_ Benzodioxofluoren-2-yl] · 3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D. 3.80 2- (4-Bromophenoxy) -acetamidamine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a , 5,5 · trimethyl-4,6-fluorenyl-1,3,2-benzodioxol-2-yl] -3 · methylbutyl] amino] carbonyl] -4 -[[Imino (trimethylamino) methyl] amino] butyl] D.3.81 2- (1-methyl-1H-fluorin-3-yl) acetamidine, N-[(1S ) -1 _ [[[(1R) 小 [(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trifluorenyl-4,6-fluoranyl-1,3,2-benzyl Dioxo-2-yl] each methylbutyl] amine] carbonyl] -4-[[imine (nitroamine ) Methyl] amino] butyl] 95014 -43-200529810 D.3.82 Hexahydro-2,5-methylalkyldioxo-3a (lH) · carboxamide, bucket [(13) 小 [[[(1 幻 -1-[(3 and 3,43,68, 7 &amp; 11) -hexahydro-3 &amp; 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (Zoylamino) methyl] Amino] butyl] D.3.83 Bicyclo [2.2.1] heptane-2-carboxamide, N- [(1S) -H [[(1R) -1-[(3 &amp; 3,48,63,7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl -1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] _carbonyl] -4-[[imino (nitroamino) methyl ] Amine] butyl] D.3.84 (RS) -2- (4-Gaphenyl) propanilamine, 仏 [(13) 小 [[[(111) 小 [(3 &amp; 3,48,63 &gt; 11) -Hydroxy-3'5,5_trimethyl-4,6_methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine Group] carbonyl] -4-[[Imine (acylamino) methyl] amino] butyl] D.3.85 (2S) -2-methylbutanamide, N-[(lS) -1 -[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl_1,3,2_benzobis Oxoborohydrin-2 · yl] -3-methylbutyl] amino] kisyl] -4 _ [[imino (acylamino) fluorenyl] amine ] Butyl] D.3.86 (4RS) -H (1,1-dimethylethoxy) -kisyl] • hexahydropyridine-4-carboxamide, [[18) -1 _ [[((111 ) -1-[(333,48,68,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline Fluoren-2-yl] -3-methylbutyl] aminoyl] -4 _ [[imino (nitroamino) methyl] amino] butyl] D.3.87 (RS) -4- Fluorenyloctylamine, N-[(1S) small [[[((lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6- Methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] chinyl] -4-[[Imine (nitroamino) [Amino] amino] butyl] D.3.88 2-fluoro-5-methylbenzidine, ^-[(18) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] Ice [[imino (nitroamino) methyl] amino] butyl] D.3.89 2- (bicyclo [2.2.1] hept-2-yl) acetamidamine, N -[(1S) -1-[[[(1R) _1- ~ [(3aS, 4S, 6S, 7aR) A hydrogen-3 ~ 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxinium fluoren-2-yl] -3_methylbutyl] amino] carbonyl] dong [[亚亚Group (Chung-yl) methyl] amino] butyl] 95014 -44-200529810 D.3.90 Cyclopropanecarboxamide, &gt; 1 _ [(13) -1-[[[((111) -1 _ [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] aminomethyl] -4-[[imine (Nitroamino) methyl] amino] butyl] D.3.91 4-ethoxybenzamide, N _ [(1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) _ hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] Jinyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.3.92 (E) _3_ (4-bromophenyl) acrylamide, hydrazine [ (13) -1-[[[((111) _1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl] amino ] Butyl] D.3.93 (2S) -2- (6-methoxyfluoren-2-yl) -propanamide, 1 ^ [(18) small [[[((11〇 小 [(335,48, 68,7 &amp;)-Liurat-3 &amp;, 5,5-Dimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3- Methylbutyl] amino] carbonyl] dong [[imino (nitroamino) methyl] amino] butyl ] D.3.94 3-Fluoro-4-methoxybenzamide, 仏 [(13) 小 [[[((11〇-1-[(3 &amp; 3,43,68,7 &amp; 11) -six Hydrogen-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) methyl] amino] butyl] D.3.95 4-fluoro-3-methylbenzamide, 仏 [(18) -1-[[[ (11〇-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride -2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.96 non-2-enoic acid Hydrazine, [(13) 小 [[((111) 小 [(3 &amp; 3,43,63,7 &amp; 1? &Gt; Hexahydro-3a, 5,5-trimethyl-4,6- 曱Alkyl · 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Jinyl] _4 _ [[Imine (acylamino) methyl] Amine] butyl] D.3.97 (E) -3- (fluoren-2-yl) acrylamidonium, N-[(1S) small [[[((1RH-[(3aS, 4S, 6S, 7aR) · Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl ] -4-[[Imino (nitroamino) methyl] amino] butyl] 95 014 -45- 200529810 D.3.98 quinoline-2-carboxamide, [[13) -1 _ [[[(111) 小 [(333,43,63 &gt; 11) -hexahydro-3a, 5,5-trimethyl- 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ) Methyl] amino] butyl] D.3.99 1- (4-methoxyphenyl) -cyclopropanecarboxamide, 1 ^ [(13) -1-[[[((111) -1-[( 3 &amp; 8,43,63,7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl]- 3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.101 3-butenylamine, hydrazone [(13) Small [[[(111) -1-[(3 &amp; 8,43,63,7 &amp; 10-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2 -Benzobenzodioxan-2-yl] each methylbutyl] amino] carbonyl; HK [imino (trifluoroamino) methyl] amino] butyl] D.3.102 tetradecane Amidine, 怵 [(18) _1-[[[(11〇 小 [(3 &amp; 8,48,63,7 &amp; 10-hexahydro-3a, 5,5-dimethyl-4,6-methyl Alkyl-1,3,2-benzodioxocarboxan-2-yl] D Wintermethylbutyl] amino group] -4-[[Imine (Amidylamino) methyl] amino ] Butyl] D.3.103 3- (1Η · indol-3-yl) -propane Amine, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino ] Butyl] D.3.104 4-phenoxybutanamine, N-[(lS) -H [[(lR) -1-[(3aS, 4S, 6S, 7aR) 4 hydrogen_3a, 5, 5 -Trimethyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] weiyl] -4-[[ Imino (acylamino) fluorenyl] amino] butyl] D.3.105 5-keto-5-phenyl-pentamidine, [[13] -1 _ [[((111) 小 [ (3 &amp; 8,48,68,7 &amp; phantom-six rat-3 &amp;, 5,5-dimethyl-4,6_methanyl-1,3,2-benzodioxoline-2 -Yl] -3_fluorenylbutyl] amino] carbonyl PK [imine (acylamino) methyl] amino] butyl] D.3.106 (2RS) -1-((1,1-di Methylethoxy) carbonyl) -hexahydropyridinecarboxamide, &gt; ^-[(13) -1-[[[(111) -1-[(3 &amp; 3,48,68,7 &amp; 11 ) -Hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] Weiyl] -4-[[Imine (nitroamino) methyl] amino] butyl] 95014 -46- 200529810 D.3.107 stilbidine stilbene-2-diethylamine, 1 ^-[(18) -1-[[[((111) -1 _ [(3 &amp; 8,48,68,7 &amp; 11) -hexahydro- 3a, 5,5-trimethyl-4,6-methylalkynyl 1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imine (nitroamino) methyl] amino] butyl] D.3.108 External stilbidine-3-Weinamine, 1 ^-[(18) -1-[[[( 1 Magic_1-[(3 &amp; 8,48,68,7 &amp; 11) -Hexahydro-3a, 5,5-dimethyl-4,6-methylalkyl-1,3,2-benzodi Oxo-2-yl] -3-methylbutyl] amino] kisyl] -4-[[imine (acylamino) methyl] amino] butyl] D.3.109 pyridine -4-carboxamide, N-[(1S) -1-[[[((1R) small [(3 &amp; 3,48,63 &gt; 11) -hexahydro-3a, 5,5-trimethyl-4 , 6-Methylalkyl-1,3,2-benzodioxoamido-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imine (acylamino) ) Methyl] amino] butyl] D.3.110 (2S) -1 _ ((1,1_: methylethoxybolyl) _hexahydropyridine-2-carboxamidide, [(18) 小 [[ [(111) -1-[(3 &amp; 3,43,63,7))-Hexahydro-33,5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (tylamino) methyl] amino ] Butyl] D.3.111 (2R) -1-((1,1-Dimethylethoxy) hexyl) -hexahydropyridine-2-carboxamide, N-[(1S) small [[[ (11〇-1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzo Dioxo-2-yl] -3-methylbutyl] aminotenyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.112 3 , 3-Difluorenyl-butylamidine, N-[(lS) -l-[[[((lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Amine) Methyl] amino] butyl] D.3.113 4-[(phenylamino) carbonyl] butanamide, [[13] 小 [[[((111) -1-[(3 &amp; 8 , 48,68,7 &amp; 1 ^)-Liurat-3 &amp;, 5,5-Dimethyl-4,6-methylalanyl-1,3,2-benzodioxolidine-2-yl ] -3-methylbutyl] amino group] ice [[imino (nitroamino) methyl] amino] butyl] D.3.114 2,2-dimethylpentylamine, N -[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2 -Benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4 _ [[imine (Nitro group) methyl] amino] butyl] 95014 -47-200529810 D.3.115 5-thien-2-yl-pentamidine, N-[(lS) -H [[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino group] ice [[imine group ( Nitroamino) methyl] amino] butyl] D.3.116 (3RS) -l-((l, lc methylethoxy)-yl) -hexahydropyridine-3-carboxamidine, 1 ^ [(13) -1-[[((111) -1-[(3 &amp; 8,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3 · methylbutyl] amino] carbonyl] -4-[[imino (alkylamino) methyl] Amino] butyl] D.3.117 8-phenyl-octylamine, [[18] small [[[(11〇 小 [(3 &amp; 8,43,63,7 &amp; 1〇-hexahydro-3a , 5,5-trimethyl_4,6_methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino group] -4-[[ Imino (nitroamino) methyl] amino] butyl D.3.118 3-[[(1,1-dimethylethoxy) carbonyl] amino] propanilamine, [[13] -1-[[[((111) 小 [(3 略 43,63,7311) -hexahydro-3 &amp;, 5,5-trimethyl • 4,6-fluorenyl-1,3,2-benzene Benzodioxo-2-yl] -3_methylbutyl] amino] carbonyl] ice [[ Iminofluorenylamino) methyl] amino] butyl] D.3.119 tridecylamidoamine, hydrazone [(18) small [[[((111) -1-[(338,48,63,7 & amp 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] Amine] carbonyl] -4-[[Iminoimidoamido) methyl] amino] butyl] D.3.120 succinamidoamine, amidine [(18) small [[[((11〇-1- [ (3 &amp; 3,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-dimethyl-4,6-methylalanyl-1,3,2-benzodioxide [Methyl] -3-methylbutyl] aminomethyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.3.121 Pentamidine, N-[(1S ) 小 [[[((111) -1-[(3 &amp; 8,43,68,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] Jinyl] -4 · [[Imine (acylamino) methyl] amino] butyl Group] D.3.122 [[[((9H-fluoren-9-yl) methoxy] Myl] amino] butanylamine, hydrazine [(13) -1-[[[(111) 小 [(333, 43,63,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 -Methylbutyl] amino] carbonyl] -4-[[imino (sonylamino) Methyl] amino] butyl] 95014 -48- 200529810 D.3.123 2- (dimethylamino) acetamidamine, N-[(1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) _ hexahydro-3a, 5, 5 -Trimethyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] several yl] -4-[[ Imino (nitroamino) methyl] amino] butyl] D.3.124 5- (4-fluorophenyl) -pentamidine, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexaazepine-3a, 5,5_trimethyl · 4,6 · methanyl_1,3,2_benzodioxine _Yl] -3-methylbutyl] amino] several groups] _4 _ [[imine (stone sylamino) methyl] amino] butyl] D.3.125 8-keto-8-phenyloctyl Hydrazine, [[13) _1 _ [[[(111) -1-[(3 狂 8,48,68,7 &amp; 1 ^)-hexaaza-3 &amp;, 5,5-difluorenyl-4, 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[iminoamidoamino] Methyl] amino] butyl] D.3.126 4- (fluoren-2-yl) butanamine, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -Hexa_3a, 5,5-Difluorenyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane [Amino] Amino] Amino [4-yl] -4-[[Imine (songylamino) methyl] amino] butyl] D.3.127 5-ketone -5- (Epiphen-2-yl) pentamidine, bucket [(13) -1-[[[(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro- 3'5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] several groups]- 4-[[Imine (nitroamino) methyl] amino] butyl] D.3.128 2- (3-Gasphenyl) acetamidamine, N-[(lS) -l-[[[ (lR) _l-[(3aS, 4S, 6S, 7aR) -Hexa-3a, 5,5-dimethyl-4,6-methylalkyl-1,3,2-benzodioxolane -2-yl] -3-methylbutyl] amino] yiyl] -4-[[imine (nitroamino) methyl] amino] butyl] D.3.129 undecylamine ， 化 [(18) 小 [[[((111) -1 _ [(3 &amp; 3,43,63,7 &amp; 10-hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino ] Butyl] D.3.130 4-heptyl benzamidine, N-[(lS) -1-[[[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4- [[Imine (nitroamino) fluorenyl] amino] butyl] 95014 -49- 200529810 D.3.131 6-phenylhexamidine, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3a, 5,5 -Trimethyl_4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino group &gt; 4-[[imine group (Linylamino) methyl] amino] butyl] D.3.132 5-phenylpentamidine, N-[(1S) small [[[((111) -1 _ [(3 略 43,63 &gt; 11) ) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino ] Carbonyl] -4-[[Imine (acylamino) fluorenyl] amino] butyl] D.3.133 10-Hydroxydecylamine, N-[(lS) -l-[[[(lR ) -l-[(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5 · trimethyl_4,6_methylalkyl-1,3,2 · benzodioxoline-2 -Yl] -3-fluorenylbutyl] amino] kisyl] ice [[imino (sonylamino) methyl] amino] butyl] D.3.134 5-keto-5- (4 -Phenylhexahydro-1,1-yl) pentanamine, N-[(lS) -H [[(lR) _l _ [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5- Trimethyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (Aminoamino) methyl] amino] butyl] D.3.135 2- (1H-tetrazol-5 ) Acetylamine, swimming [(18) -1 _ [[[(11〇 小 [(3aS, 4S, 6S, 7aR) -hexakis_3a, 5,5-dimethyl-4,6-methylalkyl -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amine Yl] butyl] D.3.136 2- (tetrazol-1-yl) acetamidamine, N-[(1S) small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -six Hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] several groups ] -4-[[Imine (songylamino) methyl] amino] butyl] D.3.137 2- (pyrimidin-2-ylthio) acetamidamine, ^ [_ [(13)- 1-[[[((111) -1-[(3 &amp; 8,48,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1, 3,2-benzodioxolane-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl Group] D.3.138 3-methylthiopropylamidine, N-[(lS) -1-[[[(lR) -1-[(3aS, 4S, 6S, 7aR &gt; ^ hydrogen-3a, 5,5 -Trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4-[[亚Amine (Serylamino) methyl] amino] butyl] 95014 -50- 200529810 D.3.139 3- (fluoren-2-ylthio) -propanilamine, 1 ^ _ [(13) -1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) -six Hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Iminoimidoamido) methyl] amino] butyl] D.3.140 2-[(phenylmethyl) thio] ethanamido, 仏 [(18) 小 [[[ (11〇-1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride -2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (acylamino) methyl] amino] butyl] D.3.141 6-ketoheptyl Amine, bucket [(18) small [[[(111) -1-[(333,43,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Hino [H-[[Iminino (stoneshominyl) methyl] amino] butyl Group] D.3.142 4- (4-Methanesulfonylphenyl) -4-ketobutylamidine, small [(3% 43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5- Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 · methylbutyl] amino] daily] -4-[[imine (Nitroamino) methyl] amino] butyl] D.3.143 ( 2S) -1-Acetyltetrahydropyrrole-2-carboxamide, 砵 [(18) -1-[[[((11〇-1-[(3 &amp; 8,43,63,7 &amp; 11)- Hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxol-2-yl] -3-methylbutyl] amino] Carbonyl] -4-[[imino (methylamino) methyl] amino] butyl] D.3.144 3-hydroxy-2,2-dimethylpropanamide, N-[(1S)- 1-[[[((1R) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3 2,2-benzodioxolane-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl ] D.3.145 2-Ethylthioacetamide, N-[(lS) -l-[[[(lR) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4 _ [[imine (Sulmonylamino) methyl] amino] butyl] D.3.146 3-ureidopropanamine, N-[(1S) small [[[(1 幻 小 [(333,48,68,7 & amp 11) -Hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] Jinyl] -4-[[Imine (Amino) methyl] Amine] butyl] 95014 -51- 200529810 D.3.147 3-methoxypropanamide, N-[(lS) _l-[[[((lR) -H (3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4-[[imino Amine) methyl] amino] butyl] D.3.148 Methylthioacetamide, N-[(lS) -l _ [[[(lR) -H (3aS, 4S, 6S, 7aR) _A hydrogen- 3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl]- 4-[[Iminoimidoamido) amido] amino] butyl] D.3.149 3H-imidazole-4-carboxamido, N _ [(1S) small [[[((lRH-[(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutane [Amino] Amino Organyl] Ice [[Iminoimidoamido) Methyl] Amino] butyl] D.3.150 7-keto-octylamine, [[13) -1 _ [[[( 111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl_4,6_methylalkyl 4,3,2-benzodioxane Oxo-2_yl] -3-amidinobutyl] amino] kisyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.151 (E)- 3- (imidazol-4-yl) acrylamide, N-[(1S) -1-[[[((1R) -1-[(3a S, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxocarbox-2-yl] -3- Methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.152 (RS), fluorfuran-3-carboxamide, N -[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl 4,6_methylalkyl-1,3 , 2-benzodioxofluoren-2-yl] each methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] D .3.153 (E) -3- (2-methoxyphenyl) acrylamidonium, [(13) small [[[(111) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5 , 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[亚Amine (nitroamino) methyl] amino] butyl] D.3.154 2-ethoxyacetamidoamine, N _ [(1S) -1-[[[(1R) small [(3aS, 4S, 6S / 7aR) -A hydrogen-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3_fluorenylbutyl ] Amino organic group] -4-[[Imine (wallylamino) methyl] amino] butyl] 95014 -52- 200529810 D.3.155 -furan-2-yl-propanamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4 · [[亚Amine (nitroamino) methyl] amino] butyl] D.3.156-(benzenesulfonyl) propanamide, N-[(lS) -H [[(lR) -l-[(3aS , 4S, 6S, 7aR) -Hexa-3a, 5,5-Dimethyl-4,6-methylalanyl-1,3,2-phenylhydrazone dioxo-2-yl] -3- Methylbutyl] amino] Jinyl] -4-[[Imino (sucralylamino) methyl] amino] butyl] D.3.157 -Aminosulfobutylamidine, N-[( 1S> H [[(1R) Small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluoranyl-1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] amino group] -4-[[Imino (alkylamino) methyl] amino] butyl] D.3.158 (4S ) -2-keto-1,3-pyrazolidine-4-carboxamide, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Yl] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.159 (2R) -1-acetamidine Tetrahydropyrrole-2-carboxamide, 1 ^-[(18) -1-[[[(111) -1-[(3 &amp; 8,48,68,7 &amp; 1 ^)-six mice-3 &amp; , 5,5-Difluorenyl-4,6-methylalanyl-1,3,2-benzodioxolane-2-yl] -3-methylbutyl] amino] jiki]- 4-[[Iminino (methylamino) methyl] amino] butyl] D.3.160-[(Ethylamino) methylthio] -propylamidine, 沭 [(13) 小 [[ [(111) -1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-3'5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone Dioxo-2-yl] -3-methylbutyl] amino] yiyl] -4-[[imine (nitroamino) methyl] amino] butyl] D.3.161 -(Ethylthio) hexylamine, N-[(1S) -1 _ [[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] kisyl] -4-[[Imine (Aminoamino) methyl] amino] butyl] D.3.162 thiophene-2-continyl) acetamidamine, [[13] 小 [[[(1 幻 -1 · [(3aS , 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3- Methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] 9 5014 -53- 200529810 D.3.163-(Ethylamido) butyramide, N-[(lS) -l-[[[(lRH-[(3aS, 4S, 6S, 7aR) -hexarat-3a, 5,5-di Methyl-4,6-methylalkynyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (Zoylamino) methyl] amino] butyl] D.3.164 (2Z) -3- (propylaminocarbonyl) -2-propenylamine, 1 ^ [(13) -1 _ [[((1 幻Small [(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxolane-2-yl ] -3-methylbutyl] amino] carbonyl] -4-[[imino (acylamino) methyl] amino] butyl] D.3.165-(octylsulfonyl) propanium Amine, ^ [(13) 小 [[[((111) -1-[(3 &amp; 8,48,68,7 &amp; 1 ^)-hexakis_3 &amp;, 5,5-dimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl; HK [imino (trimethylamino) methyl] Amine] butyl] D.3.166-(octylthio) propanilamine, N-[(lS) -l-[[[(lR) -l _ [(3aS, 4S, 6S, 7aR) · hexakis -3a, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxopentan-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[Imine group (methylamino) methyl] amino] butyl] D.3.167 2,2-Dimethylhexylamine, N _ [(1S) small [[[((lR) -1-[(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino group] several groups] -4-[[imino group ) Methyl] amino] butyl] D.3.168 -hydroxyhexamidine, 1 ^ [(13) -1-[[[(11〇-1-[(338,43,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Isopropyl] -4-[[Imine (stone stiltylamino) methyl] amino] butyl] D.3.169 -Homoisopentylamine, bucket [(18) -1-[[[(1 幻Small [(3 &amp; 3,48,63,7 &amp; 11) -Hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzodioxoborohydride- 2-yl] Each methylbutyl] amino group] [[Imine (aminyl) methyl] amino] butyl] D.3.170, Hexylamine, N-[(1S ) 小 [[[((11〇-1-[(3 &amp; 8,43,68,7 &amp; 11) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3 , 2-benzodioxofluoren-2-yl] each methylbutyl] amino] carbonyl] -4-[[imino (nitroamino) methyl] amino] butyl] 95014 -54- 200529810 D.3.171 benzopyrazole-6-carboxamide, N-[(lS) -l _ [[[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino ( Nitroamino) methyl] amino] butyl] D.3.172-(octyloxy) propanamidin, N-[(1S) small [[[((lR) -l-[(3aS, 4S, 6S , 7aR) A hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine Radical] -4-[[Imine (acylamino) methyl] amino] butyl] D.3.173-(2-keto-tetrahydropyrrole-1-yl) -acetamido, N-[(1S) -1-[[[(1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1 , 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[iminoamidoamino) methyl] amino] butyl Base] D.3.174 benzamidine, N-[(1S, 2R) -1-[[[(1R) 小 [(3 &amp; 3,43,68,7 &amp; 1〇-hexahydro-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl ] D.3.175-[2- (2-methoxyethoxy) ethoxy] acetamidamine, [[13,211) -1-[[[((111) 小 [(338,43,68,7 &amp; 1〇_hexahydro-3 &amp; 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzene弁 Dioxo-2-yl] -3-methylbutyl] amino] Weiyl] -2-Crylpropyl] D.3.176 • Phenylbutyramide, N-[(lS, 2R) _l _ [[[((lR) -l-[(3aS, 4S, 6S, 7aR) · hexazine-3a, 5,5-trimethyl-4,6_methanyl-1,3,2-benzo Dioxo-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.3.177 (4-methylphenoxy) acetamidine, N-[( lS, 2R) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylamino-1,3 , 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-trispropyl] D.3.178 Hexylamine, N-[(1S, 2R) -1-[[[((1R) 小 [(3 &amp; 8,43,63,7 &amp; 10-hexahydro-3a, 5,5-triamidino-4,6-methylalkyl-1,3, 2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.3.179 -butylphenylhydrazine, N _ [(1S, 2R) Small [[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexairon *-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2 _Benzodioxolium-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] 95014 -55- 200529810 D.3.180 Naphthalene-2-carboxamide, N-[(1S, 2R) small [[[(11〇 小 [(3 &amp; 3,48,68 &gt; 10-hexahydro-3a, 5,5-di Methyl-4,6-methylalanyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] aminoamino] -2 stilbyl] D.3.181 Hexamidine Amine, 1 ^ [(18) _1-[[[(11〇-1-[(333,43,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trisyl-4,6- Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] weiyl] -4-[[imino (nitroamino)] Yl] monthlyl] butyl] D.3.182-(4-toluenesulfonyl) acetamidamine, hydrazone [(13) -1-[[[(111) -1-[(3 &amp; 3,48, 63,7311) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.3.183 heptylamine, ^ 4 (18) _1-[[[(111) _1 -[(338,48,68,7 &amp; 11) -Hexahydro-315,5-dimethylmethanyl-1,3,2-benzodioxin-2-yl] -3- 曱Butyl] amino] -4-[[imino (nitroamino) methyl] amino] butyl] D.3.184 1- (aminomethylamido) undecylamine small- [(18) _1-[[[(11〇 小 [(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5- Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl; HK [imino ) Methyl] amino] butyl] D.3.185-(benzenesulfonyl) acetamidamine, N-[(lS) -H [[(lR) -l-[(3aS, 4S, 6S, 7aR ) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino ] Jinyl] -4-[[Imine (nitroamino) methyl] amino] butyl] D.4.1 Naphthalenesulfonamide, N-[(1S) 小 [[[(111)- 1-[(333,48,68,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline-2_ [Methyl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (nitro'ylamino) methyl] amino] butyl] D.4.2 hydrazone-2-sulfonamide , &Gt; 1-[(18) -1-[[[(111) -1-[(3 &amp; 8,48,68,7 &amp; 1〇-hexahydro-3a, 5,5-trimethyl-4 , 6-Amidinoalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino] daily] -4-[[iminoamidoamino] Methyl] amino] butyl] 95014 -56-200529810 D.4.3 Decane small sulfonamide, 乂 [(18) 小 [[[(111) 小 [(333,48,63,7311) -hexahydro 3a, 5,5-trimethyl-4,6- Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (nitroamino) methyl [Amino] amino] butyl] D.4.4 Octanesulfonamide, 怍 [(18) 小 [[[((111) -1 _ [(333,48,68,7 &amp; Hydroxy_hexahydro-3a, 5, 5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] amino group] -4 _ [[imino group ( Cylamino) methyl] amino] butyl] D.4.5 benzylsulfonamide, bucket [(13) 小 [[[(111) 小 [(333,43,63,7 &amp; 11) -hexamidine -3a, 5,5-trifluorenyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imino (trimethylamino) methyl] amino] butyl] D.5.1 (2S) -4-[[Imine (mothinoamino) methyl] amino] -2 -[(2-fluorenylmethyl) -amino] -pentamidine, N-[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl- 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] D.5.2 (2S) -4-[[imino (nitroamino ) Fluorenyl] amino] -2 · [(1-fluorenylmethyl) -amino ] -Pentamidine, N-[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl · 1,3,2- Benzodioxofluoren-2-yl] -3 · fluorenylbutyl] D.5.3 (2S) -4-[[Imine (canylamino) methyl] amino] -2- [ Undecylamino] -pentamidine, 仏 [(111) 小 [(3 &amp; 8,43,68,7 &amp; 10-hexahydro-3 &amp;, 5,5-trimethyl-4,6- Methylalkyl-1,3,2-benzodioxofluorenyl] -3-fluorenylbutyl] D.5.4 (2S) _4-[[Imino (acylamino) fluorenyl] amine [] Yl] -2-[(phenylphosphonium) amino] -pentamidine, [[11〇 小 [(338,43,63,7 &amp; 1 ^ hexahydro-315,5-trisyl-4 , 6-Amidinoalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] D.6.1 乂 [(18) -1-[[(1 step 1-[(3 &amp; 3,48,68,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trimethyl-4,6-fluorinyl-1,3,2-benzodioxane Oxal-2-yl] -3-fluorenylbutyl] amino] carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] -NH2-fluorenyl) urea 95014 -57- 200529810 D.6.2 N-[(lS) -l-[[[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4 , 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine ] Carbonyl] -4-[[imino (nitroamino) fluorenyl] amino] butyl] -Nf-phenylurea D.6.3 N-[(13) -1-[[[(111) -1-[(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-315,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline- 2-yl] -3-methylbutyl] amino] carbonyl H-[[imino (linylamino) methyl] amino] butyl] -N'-heptylurea D.6.4 1 ^ [(13) -1-[[((11〇-1-[(3 &amp; 8,48,68,7 菹 -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (co-amino) methyl] amine Yl] butyl] -N-l-theyl) urea D.6.5 ^-[(13) -1-[[[(111) -1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro -3 &amp;, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl ] -4-[[Imine (nitroamino) methyl] amino] butyl] -N1-undecyl urea D.6.6 乂 [(18,211) -1-[[[(111) -1 -[(3 &amp; 8,43,68,7311) -Hexahydro-3 &, 5,5-trimethyl-4,6-fluorinyl-1,3,2-benzodioxoborohydride · 2 · yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] undecyl urea D.6.7 &gt; ^ [(18) -1-[[[(11 1) -1-[(338,43,63,7311) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoline- 2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imine (tylamino) methyl] amino] butyl] -N '-[5- (ethoxy Carbonyl) pentyl] urea D.7.1 Dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[Imine (acylamino) fluorenyl] amino] -2-[[ (2E) -3- (2-methoxyphenyl) _1-ketoprop-2-enyl] amino H-ketopentyl] amino] each methylbutyl] D.7.2 Dihydroxyborane , [(LR) -H [(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((E) -2-methyl-3-phenylpropene (Methenyl) amino] micrositopentyl] amino] -3-methylbutyl] D.7.3 Dihydroxyborane, [(lR &gt; H [(2S) -5-[[Imine Aminoamino) fluorenyl] amino] -2-[(4- (4-methylphenyl) butylfluorenyl) amino] -1-g isopropylpentyl] amino] -3-methylbutyl] 95014 -58- 200529810 D.7.4 Dihydroxyborane, [(1R) -H [(2S) _5-[[Imine (tylamino) methyl] amino] -2-[((2RS) -2-Phenylpropanyl) amino] small ketopentyl] amino] each methylbutyl] D.7.5 dihydroxypentane, [(lR) -H [(2S) -5-[[ Amino (nitro (Methyl) amino] amino] -2-[(2- (4-isopropylphenoxy) ethenyl) amino] berberyl isoamyl] amino] -3-methylbutyl] D.7.6 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (trifluoroamino) methyl] amino] -2-[(5-keto- 5-phenylpentamyl) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.7 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[(4RS) -H (l, lc methylethoxy) carbonyl] hexahydropyridine [Amino] amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.8 Dihydroxyborane, [(lR) _1-[[(2S) -5-[[Imine (Nitroamino) methyl] amino] -2-[(4-diethylaminobenzyl) amino] small_ylpentyl] amino] -3-methylbutyl] D .7.9 Dihydroxyborane, [(lR) -H [(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((E) -2-methyl Hex-2-enyl) amino] small ketopentyl] amino] -3-methylbutyl] D.7.10 dihydroxyborane, [(lR) -l-[[(2S) -5 -[[Imine (nitroamino) methyl] amino] -2- [〇thiophen-3-carbonyl) amino] small-pentyl] amino] -3-methylbutyl] D.7.11 Dihydroxyborane, [(lR) -l-[[(2S) -5 · [[Imine (acylamino) methyl] amino] -2-[(4-isopropylphenyl) amino]] small Ketopentyl] amino] -3-fluorenylbutyl] D.7.12 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) Fluorenyl] amino] -2-[(5-methylpyridine-2-carbonyl) amino] -1S isopropylpentyl] amino] -3-methylbutyl] D.7.13 dihydroxyborane , [(LR) -l-[[(2S) -5-[[Imine (supramylamino) fluorenyl] amino] -2-[(benzylidene) amino] microketopentyl [Amino] amino] -3-fluorenylbutyl] D.7.14 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] Amine] -2-[((E) -2-butenyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] 95014 -59- 200529810 D.7.15 Dihydroxyboron Alkane, [(1R) -1 _ [[(2S) _5-[[Imine (nitroamino) methyl] amino] -2-[((E) -pent-2,4-diene 醯Group) amino] -1_ketopentyl] amino] -3-methylbutyl] D.7.16 dihydroxyborane, [(1R) -1-[[(2S) _5-[[imine (Sulmonylamino) methyl] amino] -2-[(3,3-dimethyl-butylfluorenyl) amino] -1_ketopentyl] amino] -3-methylbutyl] D.7.17 Dihydroxyboron , [(LR) -H [(2S) -5-[[Imino (tylamino) methyl] amino] -2-[[5- (2,5-dimethylphenoxy) -2,2-dimethylpentanyl] amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.18 Dihydroxyborane, [(lR) -1- [ [(2S) -5-[[Imine (nitroamino) methyl] amino] -2 _ [(2,2 · dimethylpentamyl) amino] -1-ketopentyl] Amine] -3-methylbutyl] D.7.19 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (acylamino) methyl] amino] ] -2-[[4Heptaphen-2-yl) butylfluorenyl] amino] small ketopentyl] amino] -3-methylbutyl] D.7.20 dihydroxyborane, [(lR)- l-[[((2S) -5-[[iminofluorenylamino) methyl] amino] -2-[[5- (4-fluorophenyl) pentanyl] amino] -1- Ketopentyl] amino] -3-methylbutyl] D.7.21 dihydroxyborane, [(1R) -H [(2S) _5-[[imino (sonylamino) methyl] Amine] -2-[(2,2-dimethylhexyl) amino] -1_ketopentyl] amino] -3-methylbutyl] D.7.22 Dihydroxyborane, [ (1R) -1-[[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[(hexan-2,4-enyl) amino] -1 -Ketopentyl] amino] -3-fluorenylbutyl] D.7.23 Hydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2-[[3heptaphen-2-yl) Acrylic] amino] -1-S isopropylfluorenyl] amino] -3-fluorenylbutyl] D.7.24 Dihydroxy butterflyane, [(lR) -l-[[(2S) -5 -[[Imine (acylamino) methyl] amino] -2-[(5-cyclohexylpentanyl) amino] -1-ketopentyl] amino] -3-methyl Butyl] D.7.25 dihydroxyborane, [(lR) -H [(2S) -5 _ [[imino (nitroamino) methyl] amino] -2-[((3R) _3, 7-Dimethyloctyl-6-alkenyl) amino] small ketopentyl] amino] -3_fluorenylbutyl] 95014 -60- 200529810 D.7.26 Dihydroxyborane, [(lR) -l _ [[(2S) -5 _ [[Imine (nitroamino) methyl] amino] -2-[[3-[(4-methyl Benzyl) thio] propanyl] amino] small ketopentyl] amino] -3-methylbutyl] D.7.27 dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2-[(4-pyrrole small benzamidine) amino] -1-ketopentyl] amino]- 3-methylbutyl] D.7.28 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [(5-Fluoro-2-methoxybenzylidene) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.29 Dihydroxyborane, [(1R) -1-[[((2S) _5-[[Imine (acylamino) methyl] amino] -2-[((2S) -2 · methylbutylfluorenyl) amino] small ketopentyl ] Amine] -3-methylbutyl] D.7.30 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amine Group] -2-[(cyclopropanecarbonyl) amino] _1 · ketopentyl] amino] -3-methylbutyl] D.7.31 dihydroxyborane, [(lR) -1-[[( 2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(4-ethoxybenzyl) amino] -1-ketopentyl] amino ] _3_methylbutane Group] D.7.32 Dihydroxyborane, [(lR) _l-[[(2S) -5-[[Imino (trifluoroamino) methyl] amino] -2-[((E)- 3- (4-bromophenyl) propan-2-enyl) amino] small ketopentyl] amino] -3-methylbutyl] D.7.33 dihydroxyborane, [(1R) small [[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[[(2S) -2- (6-methoxyfluoren-2-yl) -propanyl [Amino] amino] small ketopentyl] amino] -3-methylbutyl] D.7.34 dihydroxypentane, [(lR) -1-[[(2S) -5-[[imine (Nitroamino) methyl] amino] -2-[[l- (4-methoxyphenyl) -cyclopropanyl] amino] berberylamyl] amino] -3- Methyl butyl] D.7.35 Dihydroxy pentane, [(1R) -H [(2S &gt; 5-[[Imine (acylamino) fluorenyl] amino] -2-[(3-fluoro Methyl-4-methoxybenzyl) amino] small ketopentyl] amino] -3-methylbutyl] D.7.36 dihydroxyborane, [(1R) small [[((2S)- 5-[[Imine (nitroamino) amido] amino] -2-[[((E) _3- (naphthalen-2-yl) propan-2-diluted group] amino] -1- Ketopentyl] amino] -3-methylbutyl] 95014 -61-200529810 D.7.37 Dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[Imine Amino [Amino] amino] -2-[(4-fluoro_3-methylamidino) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.38 Dihydroxyborane , [(LR) _l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[[[((9Η- 苐 -9-yl) formaldehyde Oxy] chino] amino] butanoyl] amino] _1-ketopentyl] amino] each methylbutyl] D.7.39 dihydroxyborane, [(1R) -1-[[( 2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[(4-bromobenzyl) amino] -1-ketopentyl] amino]- 3-methylbutyl] D.7.40 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-] [(3-Butenefluorenyl) amino] small ketopentyl] amino] each methylbutyl] D.7.41 dihydroxyborane, [(1R) small [[(2S &gt; 5 _ [[imine (Nitroamino) methyl] amino] _2 _ [(undecyl) amino] small ketopentyl] amino] -3-methylbutyl] D.7.42 Dihydroxyborane, [ (1R) Small [[(2S) -5-[[Imine (Thirty Amino) fluorenyl] amino] -2-] [[4- (Ethylamino) butylfluorenyl] amino] -1- ¾-pentyl] amino] -3 -methylbutyl] D.7.43 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine Methyl] amino] -2-[(6-phenylhexyl) amino] small ketopentyl] amino] -3-methylbutyl]-D.7.44 dihydroxyborane, [( 1R) -1-[[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[(5-phenylpentamyl) amino] -1-one Amyl] amino] -3-methylbutyl]-D.7.45 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl [Amino] amino] -2-[(3-methoxypropylamidino) amino] -1S isopropylpentyl] amino] -3-amidinobutyl]-D.7.46 dihydroxyborane, [ (1R) -1-[[((2S) _5-[[Iminino (sonylamino) methyl] amino] -2-[[2,2-dimethyl-3- (2-fluorenyl Propenyl) -cyclopropanecarbonyl] amino] small ketopentyl] amino] _3-methylbutyl] · D.7.47 dihydroxyborane, [(lRH-[[(2S) -5-[[ Imino (nitroamino) fluorenyl] amino] -2-[(3-methoxycyclohexylcarbonyl) amino] -1-ketopentyl] amino] · 3 · methylbutyl ]-95014 -62- 200529810 D.7.48 Dihydroxyborane, [(1R &gt; 1-[[(2S &gt; 5-[[imino (nitroamino) methyl] amino] -2-[[3- (1Η-indole -3-yl) -propanyl] amino] small ketopentyl] amino] each methylbutyl]-D.7.49 dihydroxyborane, [(1R) 小 [[(2S) -5- [[Imine (nitroamino) methyl] amino] -2-[(((K5) -2-cyclopent-2-enyl-ethenyl) amino] small ketopentyl] amine Group] each methylbutyl] D.7.50 dihydroxyborane, [(lR) -1-[[(2S) -5-[[imino (squatylamino) methyl] amino] -2 -[(5-pyrimin-2-yl-pentamyl) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.51 dihydroxypentane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(6-fluorenyl-heptanyl) amino] -1-S is the same Pentyl] amino] -3-methylbutyl] D.7.52 Dihydroxyborane, [(1R) -1-[[(2S) _5 · [[Imine (Zoylamino) methyl ] Amino] -2-[(7-yl-octyl) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.53 dihydroxyborane, [( 1R) Small [[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[(hexanyl) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7 .54 Dihydroxyborane, [(lR) -H [(2S) -5-[[Iminino (methylamino) methyl] amino] -2-[(heptanyl) amino] small Ketopentyl] amino] -3-fluorenylbutyl] D.7.55 Dihydroxyborane, [(lR) -H [(2S) -5-[[Imine (acylamino) methyl ] Amine] -2-[(3-octyloxy-propionyl) amino] -1-ketopentyl] amino] -3-methylbutyl] D.7.56 dihydroxyborane, [( lR) -l-[[(2S) -5 _ [[Imine (nitroamino) methyl] amino] -2-[(benzopyrazole-6-carbonyl) amino] -1-one Amylpentyl] amino] gallylbutyl] D.7.57 dihydroxyborane, [(lR) -H [(2S) -5-[[iminofluorenylamino) fluorenyl] amino] -2-[(undec-2-enyl) amino] small ketopentyl] amino] -3_fluorenylbutyl] D.7.58 dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imino (nitroamino) methyl] amino] -2-[(9-decenyl) amino] berinopentyl] amino] -3- Fluorenylbutyl] 95014 -63- 200529810 D.7.59 dihydroxyborane, [(1R) small [[(2S &gt; 5-[[imino (nitroamino) methyl] amino]]-2- [(Tetradecanyl) amino] small ketopentyl] amino] each methylbutyl] D.8 Decylamine, [[13,211) 小 [[[ (111) -1-[(3 &amp; 3,43,68,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodi Oxyborin-2-yl] -3-methylbutyl] amino] carbonyl] _2_hydroxypropyl]-D.8.1 (2S) -2-[(benzyloxycarbonyl) amino] orthomethyl Pentamidine, Ke (13,21〇-1-[[((111) 小 [(333,43,63,7 &amp; 11) -hexahydro-3 &amp; 55,5-trimethyl-4,6- Methyl · 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl]-D.8.2 10- (1, 3-^ — gangidyl digas · iso 丨 -2-yl) -decanoic acid-vinylamine-, N-[(lS), (2R) -2-hydroxy 1-[[((111) -1- [ (3 slightly 43,68,7311) -hexahydro-3 \ 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl] -3 -Methylbutyl] aminocarbonyl] -propyl]-D.9 N-[(lS &gt; l-[[((lR) -l-[(3aS54S56S, 7aR)-^ II -3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(4 -Methylbenzylidene) amino] ethyl]-D.10 2-S-decylamidoamino-3- (hexamidineamino) -propanamide, Ke (18) -1-[[ (111) -1-[(said in 333,48,68,7) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane Wu Yi-2-yl] -3- Methylbutyl] amino] carbonyl] D.ll 2-S-decylamidoamino-3- (4-fluorosulfoamidoamino) propanamide, N-[(1S) -1- [ [(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride- 2-yl] -3-fluorenylbutyl] amino] carbonyl] D.12 2-S-decylfluorenylamino_3- (3,4-dimethoxyphenylethylfluorenylamino) propanyl Amine, N-[(lS) -l-[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl- 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] D.13 2-S-decylaminoamino (phenylureido) propyl Amidine, N-[(1S) -H [(1R) _L · [(3aS, 4S, 6S, 7aR) -hexagon-3a, 5,5_trimethyl-4,6-methylalkyl_1, 3,2-benzomonooxan-2-yl] -3-methylbutyl] amino] carbonyl] 95014 -64- 200529810 D.14 2-Aminoacetamidamine, [[18) _1-[[[(111) 小 [(338,43,68,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl -4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -4-[[imino (nitro Amino) methyl] amino] butyl], hydrochloride D.15 3-aminopropylamidamine, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3,43 , 63,7 &amp; Phenyl-hexahydro_3a, 5,5_trimethyl_4,6_methylalkyl-1,3,2-benzobenzodioxo-2-yl] -3-methyl Butyl] amino] carbonyl] ice [[imine (acylamino) methyl] amino] butyl]; hydrochloride D.15.1 (4RS) -Hydroxypyridinecarboxamide, 仏 [ (13) _1-[[[(111) -1-[(3 &amp; 3,48,68,7 &amp;! 1) -hexahydro-3 &amp;, 5,5-trimethyl-4,6_methylalkyl _1,3,2-phenylhydrazine dioxo-2-yl] -3-fluorenylbutyl] amino] chinyl] -4-[[imino (acylamino) methyl] Amine] butyl], HC1 salt D.15.2 (RS) _hexahydropyridine · 2-carboxamide, 1 ^ _ [(18 &gt; 1-[[((111) 小 [(3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amine Group] carbonyl] -4-[[imino (nitroamino) methyl] amino] Group]; HC1 salt D.15.3 (2S) -hexahydropyridine-2-carboxamide, N-[(1S) -1 _ [[[(1R) -1-[(3aS, 4S, 6S, 7aR)- Hexahydro-3a, 5,5-trifluorenyl_4,6-methylalkyl_1,3,2_benzodioxofluoren-2-yl] -3-methylbutyl] amino] Group] -4-[[Imine (acylamino) methyl] amino] butyl]; HC1 salt D.15.4 (2R) -hexahydropyridine-2-carboxamide, N-[(1S ) _1-[[[(1R) -1- — [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6_methylalkyl-1,3,2-benzene Benzodioxo-2-yl] -3-methylbutyl] amino] Jinyl] -4-[[Imine (nitroamino) methyl] amino] butyl]; HC1 Salt D.16.1 Decylamine, H [[13) 小 [[[((111) -1-[(3 &amp; 3,43,63,731〇-hexahydro-3 &amp;, 5,5-trimethyl-4, 6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] kisyl] -2- (ethylamino) ethyl] · D.16.2 Decanamidamine, 仏 [(13) 小 [[((1 化) 小 [(3 &amp; 3,43,63,7 &amp; 1〇-hexahydro-3 ^ 5,5--trisinoyl- 4,6-methylalanyl-1,3,2-phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] carbonyl] -2- (9-thienyloxy Amine fluorenyl) ethyl] -D.16.3 Decylamine, N-[(1S) small [[[(111) 小 [( 3 &amp; 3,48,63,731〇-hexahydro-3 \ 5,5 · —trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl]- 3-methylbutyl] amino] carbonyl] -2- (pentylJuryl) ethyl]-95014 -65- 200529810 D.16.4 Decamidine, N-[(1S) small [[[((111) small [(3 &amp; 8,43,68,7 &amp; 11) _hexahydro-315,5-trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2- (methanesulfonamido) ethyl] -D .16.5 Decamidine, [(13) 小 [[[(111) -1-[(333,48,63,7 &amp; 10-hexahydro-315,5-trimethyl_4,6_methane -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(ethoxycarbonyl-succinyl) -fluorenamine) Ethyl]-E.1.1 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(( 2E) -3-ethoxycarbonyl-1-ketoprop-2-enyl) amino] berberylpentyl] amino] -3-methylbutyl] E.1.2 Dihydroxyborane, [( lR) -l-[[(2S) -5 _ [[Imine (nitroamino) fluorenyl] amino] -2-[(2-pyridylcarbonyl) amino] -1-ketopentyl ] Amine] -3-methylbutyl] E.1.3 Dihydroxyborane, [(1R) -1-[[(2S &gt; 5-[[Imine (acylamino) methyl] amino] ] -2-[(4-Butylbenzyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.1.4 Dihydroxyborane, [(lR)- l-[[(2S) -5-[[Imine (acylamino) [Amino] amino] -2-[(2-fluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.1.5 Dihydroxyborane, [(1R) -1-[[((2S) _5-[[Imine (acylamino) methyl] amino] _2 · [(3- (1,3-dihydro_1,3_diketone-2H -Isolamido-2-yl) -1S isopropylpropylamino] -1-fluorenylpentyl] amino] -3-fluorenylbutyl] E.1.6 Dihydroxyborane, [(lR)- l-[[((2S) -5-[[imino (t-amino) methyl] amino] -2-[[2- (2-methoxyethoxy) ethenyl] amino] ] -1-ketopentyl] amino] -3-methylbutyl], HC1 salt E.1.7 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (Cerylamino) methyl] amino] -2-[(2-butoxyethenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E .1.8 Dihydroxyborane, [(1R) -H [(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[[2- [2- (2-methyl Oxyethoxy) ethoxy] ethoxy] ethyl] amino] _1_ketopentyl] amino] -3-methylbutyl] E.1.9 Dihydroxyborane, [(lR) -l- [[(2S) -5-[[Iminino (Renylamino) methyl] amino] -2-[[2- (Ethylamido) ethylamido] amino] -1-one Amyl] amino] -3-methylbutyl], HC1 95014 -66- 200529810 E.1.10 Dihydroxyborane, [(lR) -l _ [[(2S) -5 · [[Imine (nitroamino) methyl] amino] -2-[[4 -(Methoxycarbonyl) butylfluorenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.1.11 dihydroxyborane, [(lR) _l-[[(2S)- 5-[[Imine (nitroamino) methyl] amino] -2-[((2 · (fluoren-2-yloxy) ethenyl] amino] small ketopentyl) amino ) -3-methylbutyl) E.1.12 Dihydroxy pentane, [(1R &gt; H [(2S &gt; 5-[[imino (nitroamino) methyl] amino] -2-[( 3-thien-2-yl-propionyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.1.13 Dihydroxyborane, [(lR) -l- [ [(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2- [2- (2-Gaphenyl) ethylfluorenyl] amino] -3-methylbutyl Ethyl] HC1 salt E.1.14 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(l -Keto-4- (1-butylhexahydropyridin-4-yl) butyl) amino] -1-fluorenylpentyl] amino] -3-methylbutyl] E.1.15 Dihydroxyboron Alkanes, [(1R) -1-[[(2S &gt; 5-[[Imininofluorenylamino) methyl] amino] -2-[(l-octanesulfonyl) amino]- 1-ketopentyl] amino] -3_fluorenylbutyl], HC1 salt E.1.16 dihydroxyborane, [(lR) -l-[[(2S) -3-[(4-methylbenzene Formamyl) amino] -2-[(decanoylamino)]-1-ketopropyl] amino] -3-methylbutyl] E.1.17 Dihydroxyborane, [(1R) Small [[(2S, 3R) -3-hydroxy-2-[(decanoyl) amino] -1-ketobutyl] amino] -3-methylbutyl] E.1.18 Dihydroxyborane , [(LR) -l-[[(2S, 3R) -3-hydroxy-2-[[10- (l, 3-diketo-1,3-dihydro-isoamydin-2-yl) -Decylfluorenyl] amino] -1-ketobutyl] amino] -3-fluorenylbutyl] E.2.1 Dihydroxypentane, [(lR) -l-[[(2S) -5- [[Imininofluorenylamino] methyl] amino] -2-[(1-_yldecyl) amino] small ketopentyl] amino] -3-methylbutyl] E. 2.2 Dihydroxyborane, [(1R) small [[(2S) -5-[[imino (nitroamino) fluorenyl] amino] -2-[(octylamino) amino] small ketopentyl Ethyl] amino] -3-methylbutyl] E.2.3 Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] ] -2-[(1-phenylcyclopentylcarbonyl) amino] small_ylpentyl] amino] -3-fluorenylbutyl] 95014 -67- 200529810 E.2.4 Dihydroxy side alkane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[((2R) -2 -Phenylbutylfluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.5 Dihydroxyborane, [(lR) -1 _ [[(2S) -5 _ [[ Imino (nitroamino) methyl] amino] -2-[[4- (l, l-dimethylethyl) cyclohexylcarbonyl] amino] -1-ketopentyl] amino ] -3-methylbutyl] E.2.6 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (sonylamino) methyl] amino]] 2-[(trans-4-pentylcyclohexylcarbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.7 Dihydroxyborane, [(lR)- l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2-[(4-phenylbutylfluorenyl) amino] small ketopentyl] amino] Each methylbutyl] E.2.8 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (acylamino) fluorenyl] amino] -2-] (4- (l, l-dimethylethyl) benzylidene) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.9 Dihydroxyborane, [( 1R &gt; H [(2S &gt; 5 _ [[imino (nitroamino) methyl] amino] -2-[(nonanyl) amino] -1-benzylfluorenyl] amino] -3- Methyl butane ] E.2.10 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imino (pyridylamino) methyl] amino] -2-[(2-pyrimidine Fluorenyl) amino] -1-ketopentyl] amino] each fluorenylbutyl] E.2.11 dihydroxypentane, [(lR) -l-[[(2S) -5-[[ Amino (nitroamino) methyl] amino] -2-[(2,3-difluorobenzyl) amino] -1-ketopentyl] amino] Ethyl butyl] E.2.12 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(dodecyl) Amine] -1-ketopentyl] amino] -3-methylbutyl] E.2.13 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (Nitroamino) fluorenyl] amino] -2-[[2- (2-iodophenyl) ethylfluorenyl] amino] -1-ketopentyl] amino] each methylbutyl] E.2.14 Pendant dihydroxy, [(lR) _l-[[(2S) -5-[[Imine (Zoylamino) fluorenyl] amino] -2-[(cyclohexylcarbonyl) amino ] Sm-Homoylpentyl] Amine] -3-methylbutyl] 95014 -68-200529810 E.2.15 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(2-methylbenzene Formamyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.16 Dihydroxyborane, [(lR) -1-[[(2S) -5- [ [Imino (nitroamino) methyl] amino] -2-[(((2S) -2-phenylpropanyl) amino] -1-ketopentyl] amino] -3-methyl Butyl] E.2.17 Dihydroxypentane, [(lR) -l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2-[(2 , 2-dimethylbutylfluorenyl) amino] _1_ketopentyl] amino] _3-methylbutyl] E.2.18 Dihydroxyborane, [(lR) -H [(2S) -5- [ [Imino (nitroamino) methyl] amino] -2-[(Junlin-2-kilyl) amino] -1-fluorenylpentyl] amino] -3-methylbutyl ] E.2.19 Dihydroxyheptane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(non-2- Diluted group) Amino] -1-ganginofluorenyl] amino] -3-methylbutyl] E.2.20 Dihydroxyborane, [(lR &gt; l-[[(2S &gt; 5-[[亚Amine (Zoylamino) methyl] amino] -2-[(2-methylcyclohexanecarbonyl) amino] -1-ketopentyl] amino] Each methylbutyl] E. 2.21 Dihydroxyborane, [(l R) _H [(2S) -5-[[Imino (pyridylamino) methyl] amino] -2-[(hept-2-enyl) amino] small ketopentyl] amine Ethyl] -3-methylbutyl] E.2.22 Dihydroxyborane, [(lR) -H [(2S) -5 _ [[Imine (nitroamino) methyl] amino] -2- [[2- (3,4-dimethylphenoxy) ethenyl] amino] -1-fluorenylpentyl] aminomethylbutyl] E.2.23 Dihydroxypentane, [(1R ) Small [[((2S) -5-[[Imine (Zoylamino) methyl] amino] -2-[((RS) -4-ethyloctyl) amino] -1-one Amyl] Amine] Each methylbutyl] E.2.24 Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(Hexahydro-2,5-methanedioxo-3a (lH) -carbonyl) amino] ylfluorenyl] amino] -3-methylbutyl] E.2.25 Dihydroxyborane , [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(bicyclo [2.2.1] heptane-2-carbonyl) Amine] -1-ketopentyl] amino] -3-methylbutyl] 95014 -69- 200529810 E.2.26 Dihydroxy monoalkane, [(lR) -l-[[(2S) -5-[[Iminino (sonylamino) methyl] amino] -2-[(5-methylhexan Fluorenyl) amino H-ketopentyl] amino] -3-methylbutyl] E.2.27 Dihydroxyborane, [(111) -1-11 (23) -5-[[Imine (Nitroamino) methyl] amino] -2-[(2,4-dimethylpyrazole-5-carbonyl) amino] -1-ketopentyl] amino] -3-methyl Butyl] E.2.28 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2 _ [( 3-carbonyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.29 Dihydroxyborane, [(1R) -1-[[(2S &gt; 5 _ [[Imine (Cerylamino) methyl] amino] -2-[(2-cycloheptylethenyl) amino] small ketopentyl] amino] -3-methylbutyl] E.2.30 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(l-methylcyclopropanecarbonyl) Amine] -1-ketopentyl] Amine] -3-methylbutyl] E.2.31 Dihydroxyborane, [(lR) -H [(2S) -5-[[Imine Methylamino) methyl] amino] -2-[(3-methylbutylfluorenyl) amino] small ketopentyl] amino] -3-fluorenylbutyl] E.2.32 Dihydroxyborane [(1R) Small [[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(3-phenylpropanyl) amino] -1-_yl Amyl] amino] -3-methylbutyl] E.2.33 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl ] Amine] -2 _ [[(E) -3- (3-methylphenyl) propenyl] amino] small] aminopentyl] amino] -3_fluorenylbutyl] E.2.34 dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Iminino (stonesynamino) methyl] amino] -2-[(2-adamantane small ethyl ethenyl) Amine] -1-ketopentyl] amino] -3-methylbutyl] E.2.35 Dihydroxyborane, [(lR) -1 _ [[(2S) -5-[[Imine group ( Ethylamino) methyl] amino] -2-[((RS) _2-fluorenylbutylfluorenyl) amino] -1 · ketopentyl] amino] -3-methylbutyl] E.2.36 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (methylamino) methyl] amino] -2-[(2-phenylethylfluorenyl) amine Yl] -1-fluorenylpentyl] amino] -3-methylbutyl] 95014 -70- 200529810 E.2.37 Dihydroxyborane, [(1R) -1-[[((2S &gt; 5-[[Imine (acylamino) methyl] amino] -2-[[2- (4-methyl Oxyphenyl) ethenyl] amino] -1-ketopentyl] amino] 3-methylbutyl] E.2.38 Dihydroxyborane, [(1R) -1-[[(2S) _5 -[[Imine (nitroamino) methyl] amino] -2-[[2- (4-bromophenyl) ethylfluorenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.39 Dihydroxyborane, [(lR) -H [(2S) -5-[[Imine (nitroamino) methyl] amino] -2- [ ((RS) _4-methyloctylmethyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.40 Dihydroxyborane, [(lR) -l-[[( 2S) -5-[[Imine (acylamino) fluorenyl] amino] -2-[(2-fluoro-5-fluorenylbenzyl) amino] small ketopentyl] Amine] -3-methylbutyl] E.2.41 Dihydroxyborane, [(lR) -1 _ [[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[[2- (Bicyclo [2.2.1] hept-2-yl) ethenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.42 Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imino (trisinoamino) methyl] amino] -2-[(4-phenoxybutyridinyl) amino ketone Pentyl] amino Ethyl butyl] E.2.43 Dihydroxyborane, [(1R) -1-[[(2S) _5-[[Imino (tylamino) methyl] amino] -2-[(2- Pyridylcarbonyl) amino] small ketopentyl] amino] -3-methylbutyl] E.2.44 Dihydroxypentane, [(lR) -H [(2S) -5-[[Imine ( Nitroamino) methyl] amino] -2-[(3- # b σ tailoring) amino] small ketopentyl] amino] -3-methylbutyl] E.2.45 Dihydroxy Borane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[(tridecylenyl) amine] small ketone Ethylpentyl] amino] Ethylfluorenylbutyl] E.2.46 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Iminino (alkylamino) fluorenyl] Amine] -2-[(8-phenyloctyl) amino] -butanylpentyl] amino] Ethyl butyl] E.2.47 Dihydroxyborane, [(lR) -l-[[ (2S) -5-[[Imino (nitroamino) methyl] amino] -2-[[4- (4-Pentanesulfonylphenyl) icel-butylbutanyl] amino] small Fluorenylpentyl 1 amine] each methylbutyl] 95014 -71-200529810 E.2.48 pendant dihydroxy, [(lR) -l _ [[(2S) -5-[[imine (nitroamine Yl) fluorenyl] amino] -2-[[3- (fluoren-2-ylthio) -propanyl] amino] -1-ketopentyl] amine ] -3-methylbutyl] E.2.49 Dihydroxyborane, [(lR &gt; l-[[(2S) -5-[[Imine (nitroamino) methyl] amino]]-2 -[[2-[(phenylmethyl) thio] ethylfluorenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.50 Dihydroxypentane, [ (lR) -H [(2S) -5-[[Imine (acylamino) methyl] amino] -2-[(3-methylthiopropylamido) amino] _1_one Amyl] amino] -3-methylbutyl] E.2.51 Dihydroxyborane, [(1R) Small [[(2S) _5-[[Imine (nitroamino) methyl] amino] ] -2-[((2S) -l-Ethylfluorenyltetrahydropyrrole-2-carbonyl) amino group] berberylfluorenyl] amino] -3-methylbutyl] E.2.52 pendant dihydroxy , [(1R) -H [(2S) _5 · [[Imine (nitroamino) fluorenyl] amino] -2-[[trans-3- (2-bromophenyl) propenylfluorenyl ] Amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.53 dihydroxyborane, [(1R &gt; H [(2S &gt; 5- [imino (nitro Amino) methyl] amino] -2-[[2- (tetrazol-1-yl) ethylfluorenyl] amino] small ketopentyl] amino] -3-methylbutyl] E. 2.54 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2- (pyrimidine-2- Thiol Ethylamido] amino] -1.pentylpentyl] amino] -3-methylbutyl] E.2.55 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[ Amino (nitroamino) methyl] amino] -2-[[2- (4-ethylphenoxy) ethylfluorenyl] amino] -1-ketopentyl] amino] -3 -Methylbutyl] E.2.56 Dihydroxyborane, [(1R) _1-[[(2S &gt; 5-[[Imine (acylamino) fluorenyl] amino] -2-[[2 -(2,5-Difluorenylphenyl) ethenyl] amino] -1_ketopentyl] amino] -3-methylbutyl] E.2.57 Dihydroxyborane, [(1R) Small [[(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[(8-keto-8-phenyloctyl) amino] -1-ketopentan [Amino] amino] -3-methylbutyl] E.2.58 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) methyl] Amine] -2-[[2- (2-fluorenylthio) ethylfluorenyl] aminofluorenyl-S isopropylpentyl] amino] each methylbutyl] 95014 -72- 200529810 E.2.59 two Hydroxyborane, [(1R) -H [(2S &gt; 5-[[imino (nitroamino) methyl] amino] -2--2-[[(Ι ^)-2-cyclopentylhexyl [Amino] amino] -1-ketopentyl] Amino] -3-methylbutyl] E.2.60 Dihydroxyborane, [(lR)-: K [(2S) -5-[[Imine Base (nitrate Amino) methyl] amino] -2-[[3- (4-methylphenyl) acrylfluorenyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.61 Dihydroxyborane, [(lR) -l-[[(2S) -5-[[Imine (terminal amino) methyl] amino] -2-[[4- (4- Methoxyphenyl) -butynyl] amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.62 Dihydroxyborane, [(1R) -1-[[( 2S &gt; 5 _ [[Imine (nitroamino) methyl] amino] phenphen-3-yl-ethynyl) amino] -1-S isopropylpentyl] amine] -3-form Butyl] E.2.63 Dihydroxyborane, [(lR) _l-[[(2S) -5-[[Imine (nitroamino) methyl] amino] -2-[[2- (Dimethylamino) ethynyl] amino] -1-ketofluorenyl] amino] -3-methylbutyl] E.2.64 Dihydroxyheptane, [(1R) _1-[[(2S ) _5-[[Iminino (sonylamino) methyl] amino] -2-[[5-fluorenylthiophen-3-yl) pentyl] amino] -1-gangylpentyl ] Amine] -3-fluorenylbutyl] E.2.65 Dihydroxyheptane, [(1R) _1-[[(2S &gt; 5-[[Imine (acylamino) methyl] amino] -2-[(Ethyl) amino] -1-onepentyl] amino] -3-methylbutyl] E.2.66 Dihydroxyborane, [(1R) small [[((2S)- 5-[[Imine Methylamino) methyl] amino] -2-[(2-ethylthioethylfluorenyl) amino] -1-ketopentyl] amino] -3-methylbutyl] E.2.67 Dihydroxyborane, [(1R) small [[(2S) -5-[[imino (nitroamino) methyl] amino] -2-[(10-hydroxydecanoyl) amino] _1_ketopentyl] amino] -3-methylbutyl] E.2.68 Dihydroxyborane, [(1R) -H [(2S &gt; 5-[[Imine (acylamino)) 曱[Amino] amino] -2-[(2-methylthioethylfluorenyl) amino] -1, ylpentyl] amino] -3-methylbutyl] E.2.69 dihydroxyborane, [( lR) -l-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[[〇 repeatedphen-2-sulfonyl) ethenyl] amine Yl] -1-ketopentyl] amino] each methylbutyl] 95014 -73- 200529810 E.2.70 dihydroxyborane, [(lR) -l-[[(2S) -5-[[ Amine 0 Shawylamino) methyl] amino] -2 _ [[3- (benzenesulfonyl) propanyl] amino] small ketopentyl] amino] -3-methylbutyl] E.2.71 Dihydroxyborane, [(lR) -l-[[(2S) -5 _ [[Imine (nitroamino) methyl] amino] -2 _ [[(RS) -tetrahydrofuran-3 -Several amino groups] amino] small ketopentyl] amino] -3-methylbutyl] E.2.72 dihydroxyborane, [(1R) -H [(2S &gt; 5 · [[Imino (reminylamino) methyl] amino] -2-[(naphthalene-1-sulfonyl) amino] -1-one-ketopentyl] amine j] Each methylbutyl Group]-E.2.73 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine (nitroamino) fluorenyl] amino] -2-[(naphthalene_ 2-sulfonyl) amino] -1-ketopentyl] amino] -3-methylbutyl]-E.2.74 Dihydroxyborane, [(lR) _l-[[(2S) -5 -[[Imine (nitroamino) methyl] amino] -2-[(benzenesulfonyl) amino] -1-onepentyl] amino] -3-methylbutyl] -F.1 Decylamine, N-[(lS) -H [[(lR) -l-[(4R, 5R) -4,5-dicyclohexyl_ [1,3,2] Fluoren-2-yl] -3-methylbutyl] amino] quinyl] -4-[[imino (nitroamino) methyl] amino] butyl] · F.2 4-benzene Butylamine, N-[(1S) -H [[(1R) _H13,15-dioxy-14-borobisspiro [5 · 0 · 5 · 3] _pentadec-14-yl] -3- Methylbutyl] amino] jiki] winter [[imino (nitroamino) methyl] -amino] butyl]-or a pharmaceutically acceptable salt or free base form thereof. 83. A compound selected from: Example number Compound name D.2.6 2- [2- (2-methoxyethoxy) acetamido] acetamido, [[13) -1- [[[(lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-fluorenyl-1,3,2-benzodi Oxoborohydrin-2-yl] -3-methylbutyl] aminoorganofluorene-[[imino (nitroamino) fluorenyl] amino] butyl D.2.7 Decylamine, Ke 1-[[[((111) _1-[(3 &amp; 8,48,68,7 &amp; Phenyl-hexahydro-3 &amp;, 5,5-trimethyl-4,6-methanyl-1,3, 2-benzodioxolane-2-yl] -3-methylbutyl] amino] chino] methyl] 95014 • 74- 200529810 D.2.8 2- [2- (2-methoxyethoxy) ethoxy] acetamidamine, [1-[[[[((111) -1 _ [(333,43,68 &gt; 1〇-hexa Hydrogen-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3 · methylbutyl] amino] carbonyl ] Methyl] D.2.9 Decamidine, 乂 [(13) 小 [[[(111) 小 [(3 &amp; 3,43,63,7 &amp; 11) -hexahydro-315,5-trimethyl- 4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] several groups]-5-ureidopentyl]-D. 2.10 4-Butylbenzamide, N-[(1S) small [[[((1R) small [(3aS, 4S, 6S, 7aR) -A hydrogen-3a, 5,5_trimethyl-4, 6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -5-methylpentyl]-D.3.190 3- [4- (2-propyl) phenyl] propanamide, &gt; ^ [(18) -1-[[[(111) -1-[(3 狂 8,48,68,73 ^)-六Nitrogen-3 &amp;, 5,5-dimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Ethyl] -4-[[Imine (acylamino) methyl] amino] butyl] D.3.191 3- [4- (ethyl) phenyl] propanamide, N-[(lS) _H [[(lR) -Ray [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 · trimethyl-4,6-methylalkyl-l, 3,2-benzodi Oxylan-2-yl] -3-methylbutyl] amino] kisyl] -4-[[Imine (acylamino) methyl] amino] butyl] D.3.192 6 -Hydroxyhexamidine, 怵 [(13) 小 [[[(11〇 小 [(3 &amp; 8,43,63,7 &amp; 11) -hexahydro-3a, 5,5-trimethyl-4,6 -Methylalanyl-1,3,2_phenylhydrazine pentoxan-2-yl] -3-methylbutyl] amino] redo] -4-[[imine (acylamino) Fluorenyl] amino] butyl] D.4.6 4-butoxybenzenesulfonamide, N _ [(1S) small [[[(lRH-[(3aS, 4S, 6S, 7aR) -hexamorine-3a, 5,5-trifluorenyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -4- [[Imine (nitroamino) methyl] amino] butyl] D.4.7 4-butyl-benzenesulfonamide, N-[(lS) -l-[[[(lRH _ [(3aS , 4S, 6S, 7aR) 4 argon-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3-form Butyl] amino] kisyl] -4-[[imine (acylamino) fluorenyl] amino] butyl] D.4.8 4-pentyl-benzenesulfonamide, N-[( lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) 4 mouse-3a, 5,5-trimethyl-4,6_methanyl-1,3,2 -Phenylhydrazone dioxo-2-yl] -3-methylbutyl] aminoyl] -4-[[亚Amino group (Methylamino) methyl] amino] butyl] 95014 -75- 200529810 D.6.8 汴 [(18) -1-[[[((11〇-1-[(3 &amp; 8,43,63,731〇-hexahydro-3 &amp;, 5,5-trimethyl-4,6-methane -1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] M group] _4 _ [[imino (nitroamino) methyl] amine Yl] butyl] -N '-(4-butylphenyl) urea D.6.9 N-[(1S) small [[[(1R) small [(3 &amp; 8,48,68,7 &amp; chemical))-six Hydrogen-3 \ 5,5-trimethyl 4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl]- 4-[[Imino (wallylamino) methyl] amino] butyl] -N '_ (4-heptyloxy1phenyl) urea D.8.3 4- (orallyl-3-yl ) Benzylamine, meaning [(18,21〇-1-[[[(111) -1-[(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-trimethyl-4 , 6-Methylalkyl-1,3,2-benzyloxypentyl-2-yl] -3-methylbutyl] amino] chinyl] -2-tripropyl] D.8.4 2- Piracetam, N-[(lS, 2R) -H [[(lR) -l _ [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5_trimethyl-4,6- Methyl-1,3,2-benzodioxo-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.8.5 Tridecylamine, N-[(lS, 2R) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl_4,6_ Methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] chino] -2-hydroxypropyl] D.8.6 4-phenylbenzene Formamidine, N _ [(lS, 2R) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) -hexamorine-3a, 5,5-trimethyl-4,6 · Methenyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] yiyl] -2-transpropyl] D.8.7 2,2 Dimethyl decylamine, N-[(1S, 2R) -1-[[[((1R) -1-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethylamine Methyl-4,6 · methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] _2-hydroxypropyl] D.8.8 ( 4-phenoxy) benzamidine, N-[(lS, 2R) -H [[(lR) -1 · [(3aS, 4S, 6S, 7aR) _hexahydro-3a, 5,5-tri Fluorenyl-4,6-methylalkyl-l, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-methylpropyl] D. 8.9 5-Butyl-2-pyridinecarboxamide small-[(13,2 magic small [[[(111) small [(3 &amp; 8,43,68々11) -hexahydro-3 \ 5,5_ Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2-trispropyl] 95014 • 76- 200529810 D.8.10 4-propoxybenzamide, N _ [(lS, 2RH-[[[(lR) 小 [(3aS, 4S, 6S, 7aR) · hexahydro-3a, 5,5-trimethyl -4,6-Methylalkyl-l, 3,2-benzodioxol-2-yl] -3-methylbutyl] amino] carboxy] -2-tripropyl] D.8.11 3 -(3-pyridyl) benzamidine, [(13,211) small [[[(11〇 小 [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4 , 6-Methylalkyl-1,3,2_ phenylhydrazone dioxo-2-yl] -3-methylbutyl] amino] kisyl] -2-transpropyl] D.8.12 6-benzene Pyridylcarboxamide, bucket [(13,21〇-1-[[[(111) -1-[(3 &amp; 8,43,68,7 &amp; 11) _hexahydro-3 &amp;, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.8.13 3-propoxybenzamide, N-[(lS, 2R) -l _ [[[(lR) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5, 5- Trimethyl-4,6-methylalkyl-1,3; ^ benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-propyl] D. 8.14 1-bromofluorene-2-carboxamide, N-[(lS, 2R) -H [[(lR) -l _ [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methyl Butyl] amino] M] -2-hydroxypropyl] D.8.15 6-bromofluoren-2-carboxylic acid amine, N-[(lS, 2R) -H [[(lR) -l-[( 3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3- Methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.8.16 3 · phenylbenzidine, N-[(1S, 2R) small [[[(lR) _l _ [(3aS, 4S , 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-phenylhydrazone dioxo-2-yl] -3 · methyl Butyl] amino] carbonyl] -2-hydroxypropyl] D.8.17 4- (2-fluorophenyl) benzamide, N-[(lS, 2R) -H [[(lR) small [( 3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5_trifluorenyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl] -3 -Methylbutyl] amino] carbonyl] -2-hydroxypropyl] D.8.18 2-pyridoxamine, N-[(1S) small [[[((111) -1-[(3 &amp; 3 , 43,63,7 &amp; 11) _Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2_benzodioxoborohydrin_2_yl1-3- Fluorenylbutyl] amino] carbonylaminomethylmethylethyl] 95014 -77- 200529810 D.8.19 Decamidine, bucket [(18) -1-[[[(111) -1-[(3 &amp; 3,43,63,7311) -hexahydro-315,5-trimethyl-4, 6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-aminofluorenylethyl] D.8.20 4 -Butyl benzamidine, N-[(1S) -1-[[[(1R) small [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5_trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-aminomethylmethylethyl] D.16.6 4- Butyl benzamidine, N-[(lS) -l-[[[(lR) -H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6 -Methylalanyl-1,3,2-benzodioxolane-2-yl] -3-methylbutyl] amino] kisyl] -2 _ [(dioxylaminomethyl) ethyl ]-D.16.7 4-Butylbenzamide, N-[(1S) -1-[[[(1R) small [(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5-tri Methyl-4,6-methylalkyl_1,3,2-benzobenzodioxo-2-yl-]-3-methylbutyl] amino] carbonyl] -2- (111-0 Than salyl) ethyl] -D.16.8 Decylamine, [[13) -1-[[[(1 幻 小 [(3 &amp; 3,43,68,7 &amp; feet) _hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(fluorenylcarbonylamino) ethyl] -D.16.9 4-phenoxybenzidine, N-[(lS) -l _ [[[(lR) -l _ [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl_1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl ] Amine] carbonyl] -2-[(benzyloxycarbonylamidamine) ethyl] -D.17 4-butylbenzylamine, N-[(lS) -l _ [[[(lR) -H ( 3aS, 4S, 6S, 7aR) A Nitrogen-3a, 5,5-trimethyl-4,6-methylalkyl · 1,3,2-benzodioxo-2-yl] -3- Methylbutyl] amino] carbonyl] _2- (aminoethyl) -hydrochloride D.18 2-S- (4-butylbenzylamido) -3- (2-pyridinecarbonylamine Group)-, N-[(1S) small [[(lRH-[(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-fluorenyl-1, 3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] Jinyl] D.19 4-butylbenzamide, N-[(lS) _l_ [ [[(lR) -H (3aS, 4S, 6S, 7aR) _Hexahydro-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxoborohydride 2-yl] -3-methylbutyl] amino] carbonyl] -2- [4-fluoro-benzenesulfonamide] ethyl]-95014 -78- 200529810 D.20 4-butylbenzidine Amine, N-[(1S) -1-[[[(1R) small [(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5, 5-trifluorenyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl + 3-methylbutyl] aminomethyl] -2-[(2 , 5-Difluorenyl-2H-pyrasylamino] ethyl] -D.21 4 · Butylbenzylamine, N _ [(lS) -l _ [[[(lR) -l-[( 3aS, aS, 6S, 7aR) 4 argon-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxo-2-yl _]-3- Methylbutyl] amino] carbonyl] _2_ (4-methylphenylureidosulfonamido) ethyl]-D.22 4-phenoxybenzamide, N-[(1S)- 1-[[[(1R) small [(3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6_methanyl-1,3,2-benzodi Oxylan-2-yl] -3-methylbutyl] amino] carbonyl] -2- (3-phenyl-lunyl) ethyl] -D.23 4-butylbenzylamine , N _ [(lS) -H [[(lR) -l-[(3aS, aS, 6S, 7aR) -hexahydro-3a, 5,5-trimethyl-4,6-methanyl-1, 3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] several groups] _2_ (4_methylbenzylideneureido) ethyl] -D. 24.1 Decylamine, 乂 [(13) 小 [[[(111) 小 [(3 &amp; 3,48,63,7 &amp; 11) _hexahydro-3 &amp;, 5,5-trimethyl-4,6 -Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] several groups] -2- [4- Fluoro-benzodiazepine] ethyl] -D. 24.2 Decylamine, 1 ^ [(13) -1-[[[(1feet) -1-[(333,43,63,7 &amp; Hexahydro , 5,5-trimethyl-4,6-methylalkyl_1,3,2-benzobenzodioxo-2-yl] -3-methylbutyl] aminomethyl] -2 -[(4-Continuedamidophenyl) carbonylamido] ethyl]-D.24.3 4 · Butylbenzimidamine, N-[(1S) -1-[[[((1R) 小 [ (3aS, aS, 6S, 7aR) 4 Hydrogen-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxolium 2-methyl-]-3-methyl Butyl] amino] carbonyl] -2- (acetamido) ethyl] · D.24.4 4-butylbenzamide, N-[(lS) -l-[[[(lR)- l _ [(3aS, aS, 6S, 7aR) 4 hydrogen_3a, 5,5-trimethyl-4,6-methylalkynyl_1,3,2_benzodioxin-2-yl- ] -3_Methylbutyl] amino] Jinyl] _2- (methanesulfonamido) ethyl]-D.24.5 Butyl benzamidine, N-[(lS) -l-[[[ (lR) -l-[(3aS, aS, 6S, 7aR) A hydrogen-3a, 5,5 · trimethyl-4,6-methylalkyl-1,3,2 · benzodioxoborohydride- 2-yl-]-3-methylbutyl] amino] weiyl] _2- (propylureido) ethyl] _ 95014 -79- 200529810 D.24.6 4-Butylbenzamide, N-[(1S) small [[[((lR) -1-[(3aS, aS, 6S, 7aR) A hydrogen_3a, 5,5-trimethyl · 4,6_methylalkyl_1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] aminomethyl] -2-[(4-methylbenzene Group) Weilylamino] ethyl l · D.24.7 4-butylbenzylamine, N-[(lS) -H [[(lR) -l-[(3aS, aS, 6S, 7aR) 4 Hydrogen-3a, 5,5-trimethyl-4,6-fluorenyl-1,3,2-benzodioxofluoren-2-yl-] each methylbutyl] amino] carbonyl] -2-[(1,1-Dimethylethoxycarbonyl) amino] ethyl] -D.24.8 4-butylbenzamide, N-[(lS) -l-[[[(lR) -l-[(3aS, 4S, 6S, 7aR) 4 hydrogen_3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl ] -3-Methylbutyl] amino] Jinyl] -2- [〇thiophen-2-ylcarbonyl) amino] ethyl]-D.24.9 Decylamine, meaning [(13) -1_ [ [[(111) 小 [(3 &amp; 8,48,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzyl Dioxo-2-yl] -3-methylbutyl] amino] carbonyl] · 2- [〇thiophen-2-ylcarbonyl) amino] ethyl]-D.24.10 4-butyl Benzamidine, N-[(lS) -l-[[[(lR) _l-[(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-tri -4,6-methylalkyl-1,3,2 "benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2- (hexanoneamino) Ethyl]-D.24.11 4-Butylbenzamide, N-[(lS) -l-[[[(lR) -l- [3aS, aS, 6S, 7aR] 4 hydrogen-3a, 5, 5-trimethyl-4,6-fluorenyl 1,3,2-benzodioxofluoren-2-yl-]-3-fluorenylbutyl] amino] carbonyl] -2- (cyclo Propylcarbonylamino) ethyl] -D.24.12 4-Butylbenzamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) 4 Hydrogen-3 \ 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxolium-2-yl] -3-methylbutyl] amino] carbonyl] 2- (3-phenyl-ureido) ethyl] -D.24.13 4-butylbenzamide, N-[(lS) -l-[[[((lR) -l-[(3aS, 4S, 6S, 7aR) 4 hydrogen_3a, 5,5_trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl] each methylbutyl] Amine] carbonyl] -2 _ [(N-methyl-2-pyrrolidinylcarbonylamidoamine) ethyl]-D.24.14 4-butylbenzylamine, N-[(1S) small [[[(lR ) -l- [3aS, aS, 6S, 7aR] A Hydrogen-3a, 5,5-trimethyl-4,6-methylalanyl-1,3,2-benzodioxolium-2-yl -] Each methylbutyl] amino group] -2 _ [(3,4-dimethoxyphenyl) acetamidine ] Ethyl] - 95014 -80-200529810 D.24.15 4-Butylbenzamide, N-[(1S) -1-[[[((1R) small [(3aS, 4S, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl -4,6-Methylalkyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] aminomethyl] -2- (in the test amine amino group) Ethyl] -D.24.16 4-Butylbenzamide, N _ [(lS) -l-[[[(lR) -l- [3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5 -Trimethyl-4,6-methylalkyl 1,3,2-benzodioxofluorenyl · 2-yl-]-3-methylbutyl] amino] weiyl] -2-[(4- Sulfoamido) benzamido] ethyl] -D.24.17 4-butylbenzimidamine, N-[(1S) -1 _ [[((1R) small [3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl 1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino ] Jinji] -2-[(1Η-tetramethyl-5-yl-ethylamino) ethyl) -D.24.18 4-butylbenzylamine, N-[(lS) -l-[[ [(lR) _l-[(3aS, aS, 6S, 7aR) 4 nitrogen-3a, 5,5-dimethyl-4,6-methylalkynyl_1,3,2_benzodioxin -2-yl-]-3-methylbutyl] amino] yiyl] -2-[(4-methylphenylmethylphenylamino] ethyl]-D.24.19 Decylamine, 1 ^ [(13) 小 [[[(111) 小 [(3 &amp; 3,48,63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-tri -4,6-methylalkyl-1,3,2-benzodioxofluorenyl] -3.fluorenylbutyl] amino] M group] -2- (nicotinylketoamino) ethyl Phenyl]-D.24.20 4-butylbenzidine, N-[(lS) -l-[[[(lR) _l-[(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5 -Trimethyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino] carbonyl] -2-[(4 -(2H-tetrazol-5-yl) phenyl) carbonylamino] ethyl]-D.24.21 4-butylbenzamide, N _ [(lS) -l-[[[(lR) -l -[(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5_trimethyl-4,6-fluorenyl-1,3,2-benzodioxolane-2-yl- ] -3-methylbutyl] aminomethyl] _2 _ [(1_isoxazol-5-yl) -carbonylamino] ethyl]-D.24.22 4-butylbenzylamine, N- [(lS) -l-[[[(lR) -1-[(3aS, aS, 6S, 7aR) -A hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3 , 2-benzodioxofluoren-2-yl_] tolylbutyl] amino] carbonyl] -2-[(4-cyanophenyl) fluorenamino] ethyl]-95014 -81-200529810 D.24.23 4-Butylbenzamide, N-[(lS) -l-[[[((lR) -l-[(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5-tri Methyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] aminomethyl] -2-[(l_methyl -1H-Miso-4_) luteinylamino] ethyl] _D.24.24 4-butylbenzylamine, N-[(1S) small [[[(1R) small [(3aS, aS, 6S, 7aR) 4 Hydrogen-3a, 5,5-trimethyl-4,6 · Methylphenyl-1,3,2 · benzodioxofluoren-2-yl-] _ 3-methylbutyl ] Amine] Jinyl] _2 _ [(2-Fenphen) phenylamino] ethyl]-D.24.25 4-Butylbenzylamine, N-[(lS) -l _ [[((lR ) -l _ [(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl_1,3,2_benzodioxoborofluorene-2- -]-3-methylbutyl] amino] kisyl] -2_ (6_morpholin-4-ylamino) ethyl]-D.24.26 4-butylbenzylamine , N-[(1S) -1-[[[(1R) Small [(3aS, aS, 6S, 7aR) 4 hydrogen-3a, 5,5-trimethyl-4,6-methanyl-1, 3,2 · Benzodioxo-2-oxo-2-yl-]-3-methylbutyl] amino] jiki] -2- (2-P ratio σ fixed-4-P plug σ sitting several groups Amine) ethyl] -D.24.27 4-butylbenzamide, N-[(1S) small [[[((lR) -H (3aS, aS, 6S, 7aR ) A Hydrogen-3a, 5,5-trifluorenyl-4,6-methylalkyl-1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino ] Carbonyl] -2- (4-methylphenylureidoxanthylamino) ethyl]-D.24.28 4-phenoxybenzamide, N-[(lS) -H [[(lR ) -H (3aS, 4S, 6S, 7aR) -Hexahydro-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane [] Methyl] -3-methylbutyl] amino] yiyl] -2-[(Ethoxybenzyl with amine) ethyl]-D.24.29 4-phenoxybenzamide, N-[(lS ) _l-[[[(lR) -H (3aS, 4S, 6S, 7aR) · Hexahydro-3a, 5,5-dimethyl-4,6-fluorenyl-1,3,2-benzo Dioxo-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2- [4-fluoro-benzenesulfonamide] ethyl]-D.24.30 4-phenoxyphenylhydrazone Amidine, N-[(lS) -l-[[[(lR) -l-[(3aS, aS, 6S, 7aR) -hexahydro-3a, 5,5-triamidino-4,6-methane -1,3,2_benzodioxofluoren-2-yl-]-3_methylbutyl] aminomethyl] -2-[(2,5-dimethyl-2H-pyridine Ii) Ethylamino] ethyl] 95014 -82- 200529810 D.24.31 4-phenoxybenzamide, N-[(lS) -l-[[[(lRH-[(3aS, 4S, 6S, 7aR) -hexarat-3a, 5,5-dimethyl -4,6-methylalanyl-1,3,2-benzodioxolyl-2-yl] -3-fluorenylbutyl] amino] carbonyl] -2- (4-phenylbenzene Fluorenylamino) ethyl] -D.24.32 4-butylbenzylamine, N-[(lS) -l _ [[[(lR) _l-[(3aS, 4S, 6S, 7aR) -hexahydro -3a, 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] 2- (4-phenylbenzylamido) ethyl] -D.24.33 4-butylbenzamidoamine, N-[(lS) -H [[(lR) _l-[(3aS, 4S ,, 6S, 7aR) -Hexafluorene-3a, 5,5-trimethyl-4,6-methylamino-1,3,2-benzodioxocarbox-2-yl] -3-methyl Butyl] amino] carbonyl] -2- (3-phenylpropynamidinylamino) ethyl]-D.24.34 4-butylbenzylamine, N _ [(lS) -l-[[[ (lR) -H (3aS, aS, 6S, 7aR) 4 Hydrogen-3a, 5,5-trimethyl-4,6-methylalkyl-1,3,2-benzodioxane-2 -Yl-]-3-methylbutyl] amino] kisyl] -2- (2-Cycloyl-3-aminomethyl) ethyl]-D.24.35 Butylbenzylamine, N-[(lS) -l-[[[(lR) -l-[(3aS, aS, 6S, 7aR)-: ^-3a, 5,5-trimethyl-4 1,6-Methylalanyl-1,3,2-benzodioxocarbox-2-yl-]-3-methylbutyl] amino] kisyl] -2- (D-pyramidamine Amino) ethyl] -D.24.36 4-butylbenzamide, N _ [(lS) -l _ [[[(lR) -l-[(3aS, aS, 6S, 7aR) 4 hydrogen-3a , 5,5-trimethyl-4,6-methylalkynyl-1,3,2-benzodioxofluoren-2-yl-]-3-methylbutyl] amino]] -2- (1-methylpyridyl-hexahydropyridine-4-carbonylamino) ethyl] -D.24.37 Decylamine, &gt; 1-[(13) -1-[[[(111) -1-[(3 &amp; 3,48,63,7311) -Hexahydro-315,5-trimethyl-4,6-methylalkyl_1,3,2-benzodioxyborohydride-2- Group] _3_methylbutyl] amino] carbonyl] -2- (3-phenyl-ureido) ethyl]-D.24.38 Decylamine, N-[(1S) small [[[(111)小 [(3 &amp; 3, 63,7 &amp; 1〇-hexahydro-3 \ 5,5-trimethyl-4,6-methylalanyl-1,3,2_phenyl hydrazone dioxolane- 2-yl-]-3-amidinobutyl] amino] carbonyl] -2- (ethylamido) ethyl] -D.25.1 Decamidon, 仏 [(13) -1-[[[(( 11〇 小 [(3 &amp; 3 Deng, 63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethyl-4,6_methylalkyl · 1,3,2_benzodioxoline Fluoren-2-yl-] each methylbutyl] amino] carbonyl] -2-amino] ethyl] -hydrochloride 95014 • 83- 200529810 D.25.2 Decylamine, N-[(1S) -1-[[[((1R) 小 [(3 &amp; 3, 63,7 &amp; 11) -hexahydro-3 &amp;, 5,5-trimethylamine -4,6_methylalanyl-1,3,2-phenylhydradioxo-2-yl-]-3-methylbutyl] amino] carbonyl] -2-amino] ethyl] -Hydrochloride D.26 4-butylbenzamide, N-[(lR) -1-[[[(lR) _H (3aS, 4S, 6S, 7aR) -hexahydro-3a, 5,5 -Trimethyl-4,6-fluorenylalkyl 1,3,2-benzodioxofluoren-2-yl] -3-methylbutyl] amino] carbonyl] -2-[(4 -Methylbenzyl) amino] ethyl]-E.1.23 Dihydroxyborane, [(1R &gt; 1-[[(2S, 3R &gt; 3-hydroxy-2-[(4-phenylbutyridinyl) Amino] -1-ketobutyl] amino] -3-methylbutyl] E.1.24 Dihydroxyborane, [(lR) -H [(2S, 3R) -3-hydroxy-2- [ (Undecylaminoalkyl) amino] berinobutyl] amino] -3-methylbutyl] E.1.25 dihydroxyborane, [(lR) _l-[[(2S, 3R ) -3-Hydroxy-2-[(l-bromo · 2-methylmethylfluorenyl) amino] -1-ketobutyl] amino] -3-methylbutyl] E.1.26 Dihydroxyboron Alkane, [(1R) Small [[(2S, 3R) -3-hydroxy-2-[(6-monyl-2-fluorenylmethylamino) amino] -1-ketobutyl] amino]] 3-methylbutyl] E.1.27 Dihydroxyborane, [( 1R) -H [(2S) _3-aminomethylmethyl-2-[(decylmethyl) amino] -1-Sigylpropyl] amino] -3-methylbutyl] E.1.28 dihydroxy Borane, [(lR) -H [(2S) -3-aminomethylmethyl-2- [4-butyl (benzyl) amino] ylpropyl] amino] -3-methylbutyl Group] E.1.29 Dihydroxyborane, [(lR) -H [(2S) -2-[(decylenyl) amino] small keto-5-ureido-pentyl] amino] -3- Methylbutyl] E.1.30 Dihydroxyborane, [(lR) -l-[[(2S) -2-[(4-butylphenylfluorenyl) amino] small keto-5-ureido -Pentyl] amino] -3-methylbutyl] E.2.76 Dihydroxyborane, [(1R) Small [[(2S) -5-[[Imine (tylamino) methyl] Amine] -2 _ [[(RS) -2- (4-Gaphenyl) propanyl] amino] small ketopentyl] amino] -3-methylbutyl] E.2.77 Dihydroxy shed Alkane, [(1R) -H [(2S &gt; 5-[[Imine (nitroamino) methyl] amino] -2-[[2- (4-Bromophenoxy) ethenyl ] Amino] small ketopentyl] amino] -3-methylbutyl] E.2.78 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[Imine Methylamino) methyl] amino] -2-[[3- (4-ethylphenyl) propanyl] amino] small_ylpentyl] amino] each methylbutyl] 95014 -84 -200529810 E.2.79 Dihydroxy Gyptane, [(lR) _l-[[(2S) -5-[[Imine (acylamino) methyl] amino] -2- [3- [4- (heptyloxy) benzene Group] -ureido] -1-ketopentyl] amino] · 3-methylbutyl] E.2.80 Dihydroxyborane, [(lR) -1-[[(2S) -5-[[ Imino (nitroamino) methyl] amino] -2-[(5-ketohexyl) amino: M-ketopentyl] amino] -3-methylbutyl] E .2.81 Dihydroxyborane, [(1R) -1-[[(2S) _5-[[Imininofluorenylamino) methyl] amino] -2-[[((2RS) _H (l, lc Methylethoxy) carbonyl] hexahydropyridine-2-carbonyl] amino] small ketopentyl] amino] -3-methylbutyl] E.3.1 Dihydroxyborane, [(lR) -H [(2S, 3R) -3-hydroxy-2-[(2-naphthylmethylamino) amino] small 8-isobutylbutyl] amino] -3-methylbutyl] E.3.2 Dihydroxyborane , [(LR) -l-[[((2S, 3R) -3-hydroxy-2-[(p-tolyloxyacetamido) -1-one-butylbutyl) amino) -3-methylbutyl E.3.3 Dihydroxyborane, [(1R) -1-[[(2S, 3R) _3-Hydroxy-2-[(tridecylenyl) amino] -1S isopropylbutyl] amino] -3-methylbutyl] E.3.4 Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(fluorene-2_methoxymethylamino)] -1-ketobutyl] amino] -3-methyl Butyl] E.3.5 Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(4-phenylbenzylidene) amino] -butyralylbutyl ] Amine] -3-methylbutyl] E.3.6 Dihydroxyborane, [(lR) -H [(2S, 3R) -3_hydroxy_2-[(2,2dimethylfluorenyl) Amine] small ketobutyl] amino] -3-methylbutyl] E.3.7 Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3-hydroxy-2- [ (4-phenoxybenzyl) amino] -1-ketobutyl] amino] -3-methylbutyl] E.3.8 Dihydroxyborane, [(lR) -1 _ [[( 2S, 3R) -3-hydroxy-2-[[4- (l-propoxy) butylbenzylidene] amino] small ketobutyl] amino] -3-methylbutyl] E. 3.9 Dihydroxyborane, [(lR) -H [(2S, 3R) -3_hydroxy-2 _ [(3_pyridin-3-yl-benzylidene) amino] -1-ketobutyl] Amine] -3-methylbutyl], hydrochloride E.3.10 dihydroxyborane, [(lR) _1-[[(2S, 3R) -3-hydroxy-2-[(3-propoxy -Phenylphenyl) amino] small ketobutyl] amino] -3-methylbutyl] E.3.11 Dihydroxyborane, [(1R) -1-[[(2S, 3R) each hydroxyl group -2-[(3-Phenylbenzyl) amino] -1-ketobutyl] amino] -3-methylbutyl] 95014 -85- 200529810 E.3.12 Dihydroxyborane, [(1R) small [[((2S, 3R) -3-hydroxy-2-[(4- (2-fluorophenyl) benzyl) amino) amino] -1-one Butyl] amino] -3-methylbutyl] E.4 Dihydroxyborane, [(lR) -1-[[(2S, 3R) -3_hydroxy-2-[[4- (3 -Said pyridyl) benzamyl] amino] -1--butylbutyl] amino] -3-methylbutyl] E.4.1 Dihydroxyborane, [(1R) -1-[[( 2S, 3R) _3-Hydroxy-2-[(24 carbonyl) amino] -1-ketobutyl] amino] -3 · fluorenylbutyl] E.4.2 Dihydroxyborane, [(lR) -l _ [[(2S, 3R) -3-hydroxy-2-[(5-butyl4pyridin-2-carbonyl) amino] -1-ketobutyl] amino] -3-methylbutyl ] E.4.3 Dihydroxyborane, [(lR) -l-[[(2S, 3R) -3-hydroxy-2-[(6 · phenyl-speakpyridin-2-yl) amino]] -Fluorenylbutyl] amino] -3-methylbutyl] E.5 Dihydroxyborane, [(lR) -1-[[(2S) -3- (2-pyridinecarbonylamino)- 2-[(4-Butylbenzylamine)]-1-ketopropyl] amino] -3-methylbutyl] E.5.1 Dihydroxyborane, [(lR) _l-[[ (2S) -3- (Ethylamido &gt; 2-[(decylamido)] small ketopropyl] amino] -3-methylbutyl] E.5.2 Dihydroxymethane, [( lR) -l-[[((2S) -3_ (propylureido) -2-[(4-butyl) -benzyl Amine] -1-amidinopropyl] amino] -3-methylbutyl] E.5.3 Dihydroxyborane, [(lR) -l-[[(2S) -3- (methanesulfonamide Group) -2-[(4-butyl) -benzylamido] -1--propylpropyl] amino] -3-amidinobutyl] E.5.4 Dihydroxyborane, [(lR) -l-[[((2S) -3- [2- (lH-pyrazole) ethyl] -2-[(4-butyl) -benzylideneamino] small ketopropyl] amino]] 3-methylbutyl] E.5.5 Dihydroxyborane, [(lR) -l-[[(2S) -3- (methanesulfonamido) -2-[(4-butyl) -benzyl Fluorenylamino] small ketopropyl] amino] -3-methylbutyl] E.5.6 Dihydroxyborane, [(lR) -H [(2S) -3-[(fluorenylcarbonylcarbonylcarbonyloxy) Aminoamino] -2-[(4-butyl benzamidineamino)] small ketopropyl] amino] -3-methylbutyl) E.5.7 Monoalkyl, [(lR) -l-[[(2S) -3 _ [(Epiphenylyl) amino] -2-[(4-butylbenzylamino)]-1-ketopropyl] amino] -3 -Methylbutyl] E.5.8 Dihydroxyborane, [(lR) -1-[[(2S) -3- (ethylamidoamino) -2_ [4-butyl-benzamidoamine]] Small ketopropyl] amino] methyl butyl] E.5.9 Dihydroxyborane, [(lR) -l-[[(2S) -3-[(Epiphen-2-ylcarbonyl) amino] ;]] _ 2 _ [(Decylamino)] small ketopropyl] amine ] Each methylbutyl] E.5.10 Dihydroxyborane, [(lR) -l-[[(2S) -3- (Hexamidineamino) -2 _ [(4-butylbenzylamine) ] -1-ketopropyl] amino] each methylbutyl] 95014 -86- 200529810 E.5.11 Erjingjiyuan, [(lR) _l-[[(2S) -3- [4-Gas-Benzylamino]] · 2-[(4-butylbenzyl) amino] -1-Ketopropyl] amino] -3-methylbutyl] E.5.12 Two-stage sintering, [(lR) -1-[[(2S) -3- [4-Gas-Benzene continued Fermented amine] -2-[(decanol) amino] small ketopropyl] amino] _3-methylbutyl] E.5.13 Dihydroxyborane, [(lR) -l-[[(2S ) -3- (hexanoneamino) &gt; 2-[(decanoylamino)] minor group propyl] amino] -3-methylbutyl] E.5.14 Dihydroxyborane, [(1R ) Small [[((2S) -3- (hexanoneamino)) _ 2-[(cyclopropylcarbonylamino)] small ketopropyl] amino] each methylbutyl] 3-methylbutyl] Amine] carbonyl> 2- (cyclopropylcarbonylamino) ethyl] -E.5.15 Dihydroxyborane, [(lR) -l-[[(2S) -3-[(3,4-dimethyl Oxyphenyl) acetamido] -2-[(4-butylbenzylamido)] small ketopropyl] amino] · 3-methylbutyl] E.5.16 dihydroxyborane , [(1R) Small [[(2S) -3- [lN-methyl-2-pyrrolylcarbonylamino]]-2-[(4-butylbenzylidene) amino] -1-one Propyl] amino] -3-methylbutyl] E.5.17 dihydroxyborane, [(lR) -1-[[(2S) -3- [4-aminosulfonylphenylphenylamino]] -2-[(4-butyl benzamidine ) Amino] -1-amidinopropyl] amino] -3-methylbutyl] E.5.18 Dihydroxyborane, [(lR) -1 _ [[(2S) -3- (nicotinylfluorenyl Amine) -2-[(4-butylbenzylamido)] small ketopropyl] amino] -3-amidinobutyl] E.5.19 dihydroxyborane, [(lR) -1 -[[(2S) -3- (3-phenylureido) -2- (4-butylphenyl f amido) -1-ketopropyl] amino] -3-methylbutyl] E .5.20 Dihydroxyborane, [(1R) small [[(2S) -3-[(4-fluorenylsulfonyl) benzylamine]] _ 2 _ [(4_butylbenzylamino)] small Ketopropyl] amino] -3-methylbutyl] E.5.21 Dihydroxyborane, [(lR) -1-[[((2S &gt; 3- (3-phenylureido) -2- (decyl Fluorenylaminoketopropyl] amino] -3 · methylbutyl] E.5.22 dihydroxyborane, [(lR) -1-[[(2S &gt; 3- (nicotinylfluorenylamino)] -2_ (decylenylamino) berberylpropyl] amino] 3-methylbutyl] E.5.23 Dihydroxypentane, [(lR &gt; l-[[(2R) -3- (4- Methylphenylcarbonyl) -2- (decanoylamino) -1-fluorenylpropyl] amino] -3-fluorenylbutyl] E.5.24 Dihydroxyborane, [(lR &gt; l- [ [(2S &gt; 3- [4- (lH-tetrazolyl) _phenylcarbonylamino]]-2-[(4-butylbenzylamido)]-1-ketopropyl] amino] -3-A 200.52981 million butyl 195014-87- E.5.25 Dialkyl radical burning, [(lR) -l-[[(2S) -3- (2-iso4-fluorenylcarbonamino) -2--2-((4-butylbenzylamino) )] Small ketopropyl] amino] -3-methylbutyl] E.5.26 Diyl side burning, [(lR) _1-[[(2S) -3- [l-methyl-1H_imid]. 4-Amine sulfonyl] -2-[(4-butylbenzylidene) amino] -1-ketopropyl] amine / 'yl] -3_methylbutyl] E. 5.27 After the basal firing, [(lR) -l-[[(2S) -3- [6-morpholin-4-yl-p ratio. Amine-3-aminosulfonyl] -2-[(4-butylbenzylidene) amino] ylpropyl] amino] -3-methylbutyl] hydrochloride E.5.28 di 1½ • Base shed, [(lR) -l-[[(2S) -3_ (6-Morpholin based on fermentation amines) -2-[(4-butylbenzylidene) amino]]-1- Ketopropyl) amino) _3_methylbutyl) E.5.29 Dioxin, [(lR) -l-[[(2S) _3- (4- (l, 3_dimethyl_1Η) -ρ 比 嗤 -5_ carbonylamino) -2-[(4-butylbenzylidene) amino] -1-ketopropyl) amino) -3-methylbutyl] hydrochloride E .5.30 Two. Basic greenhouse, [(lR) -l-[[(2S) -3- [4-fluoro-phenylphenanthramine] -2-[(4-phenoxybenzyl) amine) ] -1-ketopropyl] amino] -3-methylbutyl] E.5.31 Dihydroxyborane, [(lR) -1-[[(2S) -3_ (4- (l, 3- Dimethyl-1H-pyrazole-5_ carbonylamino) -2-[(4 · phenoxyphenylamidino) amino] -1_ketopropyl) amino) -3-methylbutyl ] Carbonylamino] ethyl] _ E.5.32 Dihydroxyheptane, [(lR) -H [(2S) -3- (4-phenylureido) _2-[(4_phenoxybenzyl) ) Amino] -1-ketopropyl] amino] -3-methylbutyl] E.5.33 Dihydroxyborane, [(lR) -1-[[(2S) -3- (4-benzene Benzamidine) -2-[(4-butylbenzene Fluorenyl) amino] -1-ketopropyl) amino) -3-fluorenylbutyl) E.5.34 dihydroxyborane, [(lR) -H [(2S) -3- (4-benzene Phenylbenzylamine) -2-[(4-phenoxybenzyl) amino] -1-ketopropyl) amino) -3-fluorenylbutyl) E.5.35 Dihydroxyborane , [(1R) Small [[(2S) -3- (phenylpropylamidoamine) -2-[(4-butylphenylamidino) amino] -1-S isopropylpropyl) amino) 3-methylbutyl) E.5.36 dihydroxyborane, [(lR) -l-[[(2S) -3- (4-methylbenzenesulfonyl) -ureido] -2-[( 4-butylbenzylidene) amino] -1-ketopropyl] amino] -3-methylbutyl] 95014 -88- 200529810 鬌 Ε.5.37 Dihydroxyborane, [(lR) -H [(2S) -3- (4- (2- (4-pyridylfluorene, 3-thiazole-4-carbonylamino))-2- [ (4-Butylbenzyl) amino] small ketopropyl) amino] -3-methylbutyl) E.5.38 dihydroxyborane, [(lR) -l-[[(2S) -3- (l-methanesulfonylhexahydropyridine-4-carbonylamino) -2-[(4-butylbenzylamino)] small ketopropyl] amino] -3-methyl Butyl] Ε.5.39 dihydroxyborane, [(lR) _l-[[(2S) -3-[(2_pyrimidine) phenylamino]] &quot; · 2-[(4-butylbenzene Methylamino)]-1-Aminopropyl] amino] Ethylmethylbutyl] E.5.40 Dihydroxyborane, [(lR) -l-[[(2S) -3- (4- ( lH-1,2,4-triazole small group) benzamidine)]-2-[(4-butyl benzamidine) amino] -1-ketopropyl] amino] -3-methyl Butyl] hydrochloride E.5.41 Dihydroxyborane, [(lR) _1-[[(2R) -3- (4-methylphenylcarbonyl) _2_ (decylamidoamino) -1-one Propyl] amino] -3-methylbutyl] E.5.42 dihydroxyborane, [(1R) -H [(2S) _3_ (4-phenylureido) -2- (decylamino) -1S isopropylpropyl] amino] each methylbutyl] E.5.43 dihydroxyborane, [(1R) -1-[[(2S) each ethylamido-2-decanoylamino 1-1-ketopropyl] amino] -3-fluorenylbutyl 1 F.2.1 4-butylbenzylamine, N-[(1S, 2R) -1-[[[((1R) 小 [ 13,15-dirotyl spiro [5.0 · 5 · 3] pentadec-14-yl] -3-methylbutyl] amino] several groups] propyl]------ or its pharmacy Acceptable salt or free base form. 84. A composition comprising a compound according to any one of claims 1 to 83 and a pharmaceutically acceptable carrier. 85. An in vitro method for inhibiting the activity of a protein degrading body, comprising connecting a compound according to any one of the items 1-83 to the protein degrading body 86. A pharmaceutical composition for treating cancer, comprising a therapeutic agent An effective amount of the compound is as described in item 1-83. 8λ If Qingqiu X, please use the pharmaceutical composition for treating cancer, wherein the cancer is from the skin, prostate, colorectum, pancreas, kidney, Yin nest, breast shoulder 95014 -89- 200529810 liver, tongue, lung and smooth muscle organization. 88. The pharmaceutical composition for treating cancer according to claim 86, wherein the cancer is selected from leukemia, lymphoma, non-Hodgkin lymphoma, myeloma, and multiple myeloma. 89. The pharmaceutical composition for treating cancer according to claim 86, further comprising a compound according to any one of the claims __82 in a therapeutically effective manner, and using one or more antitumor or anticancer agents and / or Radiation Therapy. 90. An in vitro method for inhibiting degradation of a proteinaceous shell, which comprises contacting a protein degrading body capable of degrading the proteinaceous shell with a compound as claimed in any one of claims 83. 91. The method of claim 9G, wherein the protein is labeled with ubiquitin. 92. The method of claim 90, wherein the protein is yang. 93.-A pharmaceutical substance for treating accelerated or enhanced proteolysis', which comprises a therapeutically effective amount as claimed in one of the items ... one of # 物 0 鳓 9 \ A pharmaceutical composition for inhibiting the activity of a transcription factor, which is known to be a compound of any one of the items 1-83. 95 dr medicinal composition for treating diseases or disorders, the disease or cancer: self-immunity or whole virus infection, or due to transplant rejection 1 psoriasis, restenosis and autoimmune / osteoporosis, bone and joint 1 including households For the treatment of inflammatory diseases caused by M dendroic diseases, the oral treatment of h is the same as the request item ⑷H 96.—A method for preparing a compound of formula (11):, Huakoucai 95014 -90- 200529810 (Π) where: D is absent, 0, S, NR16 or CR15eRi5f; R is ^ · ^ alkyl, c2-C8 alkenyl, C2-C8 alkynyl, or c3-C7 cycloalkyl; R'R 5b, R15c, R15d, R15e, R15f are each independently fluorene, Ci-Cio alkyl C3 &lt;: 7 ^ alkyl, aryl or heteroaryl, wherein the C plant CiO alkyl, cycloalkyl, aryl or heteroaryl is optionally 1, 2, 3 or 4 _ groups, ( VQ alkyl, (^ 〇4alkoxy, (^^ alkoxy), 0H, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; Xia or Rih with Rub and other Wait for the connected c atoms to form a fluorenyl group or a 3- to 10-membered heterocyclic alkynyl group, each of which is optionally 1, 2, 3, or 4 halo groups, A-(: 4 alkyl, .- ( ^ Alkoxy, Ci_Q_alkoxy, 0h, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; or R15. Formed together with riw and the c atom to which they are attached A cycloalkyl group or a 3 · to 1G_M heterocyclic alkyl group, each of which is optionally a halo group, a 2, 3, or 4 halo group, a Q-Q alkyl group, a Cl-C4 alkoxy group, a & haloalkoxy group, H, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; or 151 &quot; and feet 15. and the C atom to which they are connected and inserted into the D part Groups, which together form an aryl, heteroaryl, C3-Cl () cycloalkyl or 3- to 10-membered heterocycloalkyl group, each of which is optionally halved, 2, 3, or 4 halo, alkyl, Cl % 95014 -91 · 200529810 Rhooxyalkoxy, 0H, amine, alkylamino, dialkylamino, aryl or heteroaryl substitution; R16 is alkyl; and P and q are each independently 1, 2 or 3; which includes a) a diol of formula (nb): With the appropriate formula (Π-a) trialkoxyborane: r17〇 / OR17 B〆 OR17 (Π-a) Each R in eight is independently a q 0 alkyl group or a c 3 0 cycloalkyl group, and is reacted under conditions and conditions suitable for forming an intermediate of formula (II-C) R17〇 \ P And b) using an intermediate of formula (II-C) with a reagent of formula Rl CH2 MXhai, where M is a metal and Xhal is a halogen, or 丨) formula Rl reagent, in a compound suitable for forming a compound of formula (Π) Reaction under time and conditions. 97. The method of claim 96, wherein R17 is Ci-C4 alkyl. 95014 -92- 200529810 98. The method of claim 96, wherein R17 is isopropyl. &quot; · The method of claim 96, wherein the diol of formula (Π-b) is pinanediol, pinacol, 12-ethanediol, 1,3-propanediol, 1,2-propanediol, 2, 3-butanediol, 1,1,2,2-tetramethylethanediol, 1,2-diisopropylethanediol, 5,6-decanediol, I2 · dicyclohexyl Ethanediol, dicyclohexyl-1,1'-diol, diethanolamine or 1ί 2_diphenyl_1,2_ethanediol. 100. The method of claim 96, wherein the diol of formula (Π-b) is a pinanediol. Meal 101. The method of claim%, wherein R1 CH2MXhal is R1 Ci ^ MgBr. 102. The method of claim 96, wherein Ri is isopropyl. 103. The method of claim 96, which is used to prepare a compound of formula (IH): It includes a) reacting (1S, 2S, 3R, 5SM +)-alkanediol with triisopropoxyborane at a time and under conditions suitable for forming an intermediate of formula (II-ii): And b) reacting an intermediate of formula (iHi) with isobutylmagnesium bromide at a time and under conditions suitable for forming a compound of formula. 104 · —type compound (iHi) · 95014 • 93- 200529810 105. A method for preparing a compound of formula (I): • ① where: Rl is CrC6 alkyl, C2-C6 alkenyl, c2-c6 alkynyl or c3-c7 cycloalkyl; R2 is -ch2nh2; Q is -B (〇Rl4) 2 or cyclic dihydroxyborane Ester, wherein the cyclic dihydroxyboron Sg contains 2 to 20 slave atoms, and optionally contains a hetero atom which may be N, S or 0; R4 is C1-C4 alkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl; try x is RAC (= 0)-; RA is alkyl substituted by R2G as appropriate; R2G is selected as appropriate Substituted c2-c2G alkenyl; c2-c2G alkynyl optionally substituted by R2G; optionally carbocyclyl substituted by 1-5 R2 1; or heterocarbocyclic substituted by 1-5 R21 if appropriate; R2Q The system is selected from: -cn, i-based,! Alkyl_, Ci-C4 alkyl, C2-C4 alkenyl, C2_q alkynyl, -C02 Η, -c (= 0) nh2, &lt; 0 = 0) 11, 95014 -94- 200529810 -S (= 0) NH2, -S (= 0) 2NH2, _OH, -SH, _NH2, -NH (hexyl), -N (alkyl) 2, -NHC (= 0) NH2, -NHCH)) R2Ga, -NHC (= O) OR20a, -OR2 0 a, -SR2 0 a, -S (= 0) R2 0 a, -S (= 0) 2 R2 0 a, -S (= 〇) 2 -NHR2 0 a, -SC (-O) R20a ^ -C (= O) R20a &gt; -C (= O) NHR20a ^ -C (= O) O-R20a '-NHS (= O) 2R20a, -NHR20b, neighbor Xylylenediamine,-(0-alkyl) r, -0-alkyl-OH,-(0-alkyl) r-0H, -OR20c, -SR20c, -0-alkyl_r2. c, each alkyl group -R20c, -S (= O) -R20c, -S (= O) 2-R20c, -S (= O) 2-NHR20c, -SC (= O) R20c, -C (= O ) R20c, -C (= O) OR20c, -C (= 0) NHR2Ge, optionally a carbocyclic group substituted with 1-5 R2 1; and optionally a heterocarbocyclic group substituted with 1-5 R2 1 ; R2 0 a is Ci-C2o alkyl, C2-C2o diluted or C2-C2o alkynyl; wherein the alkyl, alkenyl or alkynyl is optionally one or more halo groups, Ci -c4 Alkyl, aryl, heteroaryl or -NHR2Gb substitution; R2 ^ b is an amine protecting group; R2Ge is a carbocyclic group optionally substituted with 1-5 R22; or optionally 1-5 R2 2 Heterocarbocyclyl; R21 is selected from the group consisting of: Ci (20 alkynyl, C2-C2 〇 浠Group, C2 -C2 alkynyl, Ci -C2 alkynyl, Ci -C20 thioalkoxy, -OH-CN, halo, haloalkyl, -NH2, -NH (alkynyl), -N ( Alkynyl) 2, -NHC (= 0) 0-alkyl, -NHC (= 〇) alkyl,, C (= 0) 0-alkyl, -C (= 0) alkyl, -S (= 0 ) -Hyunyl, -S (= 〇) 2 -Yuanji, -S (= 0) _aryl, -S (= 0) 2-aryl, optionally a carbocyclic group substituted with 1-5 R22 And optionally a heterocarbocyclic group substituted with 1-5 R22; R22 is selected from the group consisting of: 95014 • 95- 200529810 CVCio alkyl, c2-c1G alkenyl, c2-c1G alkynyl, phenyl, aryl, thiol, thiol, thiol, amine, amine, diamine, carboxyl, alkane -Oc (= o)-, alkyl-c (= o)-, aryl-oc (= o)-, alkyl-0C (= 0) NH-, aryl-0C (= 0) NH- , Alkyl-C (= 0) NH-, alkyl-C (= 0) 0-, (alkyl-0) r-alkyl, ΗΟ- (alkyl-0) r-alkyl-, -OH , -SH, -CN, -N3, _CNO, -CNS, alkyl-S (= 0)-, alkyl_S (= 0) 2-, H2NS (= 0) _, and H2NS (= 0) 2- And r is 2, 3, 4 or 5; which includes: making a compound of formula (I), where R2 is -CH2 NH-C (= 0) 0CH2 (C6 H5); and a suitable hydrogenation agent, where appropriate to form the formula (I) The reaction of the compound under time and conditions, wherein R2 is -CH2NH2, provided that the hydrogenation agent is selective for the benzyloxycarbonyl group of R2. 106. The method of claim 105, wherein the hydrogenation agent is 10% Pd / C and HC1 in 1,4-dioxolane. 95014 -96 · 200529810 7. Designated representative map: (1) Designated representative map in this case is: (none) (II) Brief description of the component symbols of this representative map: • 8. If there is a chemical formula in this case, please disclose the best display of the invention Chemical formula of characteristics: 95014